Nov. 2019, 日本放射線影響学会賞, DNA二重鎖切断修復機構に基づく放射線誘発突然変異および放射線感受性の研究, 一般社団法人 日本放射線影響学会
田内 広
Japan society

2018, 平成29年度特別研究員等審査会専門委員（書面担当）表彰, 日本学術振興会
Others

2003, （財）放射線影響協会奨励賞

2002, 日本癌学会奨励賞

1999, 日本放射線影響学会奨励賞

Possible existence of dose-rate threshold for mutation induction by chronic low-dose-rate gamma-rays
Haruki Nagashima; Kenshi Komatsu; Hiroshi Tauchi, Last, Abstract

To assess the biological effects of low-dose and low-dose-rate radiation, we established a sensitive assay system for detecting somatic mutations in hypoxanthine-phosphoribosyltransferase 1 (HPRT1) gene. In this study, we investigated the dose-rate effects of mutagenesis by gamma irradiation at dose-rates of 6.6, 20 and 200 mGy d−1. We identified a potential inflection point in the gamma-induced mutant frequency, which ranged between 6.6 and 20 mGy d−1. In addition, the mutant spectrum was not different from that of the non-irradiated control at all dose-rates. Compared with previous studies with low-concentration HTO exposure, mutant frequencies were similar, but mutant spectrum showed different trends, especially at high-dose-rates (200 mGy d−1). These observations indicate the presence of potential mechanistic differences in mutagenic events between tritium beta and gamma-rays., Oxford University Press (OUP)
Radiation Protection Dosimetry, 13 Nov. 2024, [Reviewed]

Effect of PI3-kinase inhibitors on DNA double strand break repair pathways: observations using a site specific DSB induction system
Tomoki Myodo; Yuki Sakamoto; Keita Sato; Honami Kobayashi; Kenta Iijima; Kenshi Komatsu; Shinya Matsuura; Hiroshi Tauchi, Last, Abstract

We established two types of site-specific DNA double strand breaks (DSB) induction systems to elucidate factors which affect the efficiency or quality of DSB repair. For mutation assays, a site specific DSB was generated by the transient expression of a zinc finger nuclease which targets the human HPRT1 gene. A cell line in which time and site specific DSBs can be generated in a HR reporter construct was used for homology-directed repair (HR) analysis. By using these two systems, we investigated the effects of PI3-kinase inhibitors on the efficiency and quality of DSB repair. Ataxia telangiectasia mutated (ATM) kinase inhibition resulted a decrease in mutant frequency and a slight increase in deletion-type mutations accompanied by microhomology. Furthermore, the HR frequency increased significantly when ATM kinase activity was inhibited. Thus, ATM kinase activity might be involved in the suppression of DSB end resection, and this may promote DSB repair through canonical non-homologous end joining., Oxford University Press (OUP)
Radiation Protection Dosimetry, 13 Nov. 2024, [Reviewed]

Phosphorylation dynamics and kinase interaction in mRNA transcription-associated kinases: Autophosphorylation of CDK12 and its modulation by CDK7 and CDK9.　　　　　　　　　　　　　　　
Yamakawa H.; Ebara S.; Yoshida M.; Yamamoto K.; Hayashi K.; Shimokawa K.; Araki S.; Tauchi H.; Morishita D., Corresponding
BPB Reports, Sep. 2024, [Reviewed]

Interaction of CDK12 with NXF1 is a new node for the linking mechanism between transcription and transportation of mRNA
Shunsuke Ebara; Misaki Yoshida; Hiroko Yamakawa; Kenichiro Shimokawa; Yasumichi Inoue; Hiroshi Tauchi; Daisuke Morishita, Corresponding, Elsevier BV
Biochemical and Biophysical Research Communications, Aug. 2024, [Reviewed]

Establishment and activity of the planning and acting network for low dose radiation research in Japan (PLANET): 2016–2023
Yutaka Yamada; Tatsuhiko Imaoka; Toshiyasu Iwasaki; Junya Kobayashi; Munechika Misumi; Kazuo Sakai; Takashi Sugihara; Keiji Suzuki; Hiroshi Tauchi; Hiroshi Yasuda; Shinji Yoshinaga; Megumi Sasatani; Satoshi Tanaka; Kazutaka Doi; Masanori Tomita; Daisuke Iizuka; Shizuko Kakinuma; Michiya Sasaki; Michiaki Kai, Abstract

The Planning and Acting Network for Low Dose Radiation Research in Japan (PLANET) was established in 2017 in response to the need for an all-Japan network of experts. It serves as an academic platform to propose strategies and facilitate collaboration to improve quantitative estimation of health risks from ionizing radiation at low-doses and low-dose-rates. PLANET established Working Group 1 (Dose-Rate Effects in Animal Experiments) to consolidate findings from animal experiments on dose-rate effects in carcinogenesis. Considering international trends in this field as well as the situation in Japan, PLANET updated its priority research areas for Japanese low-dose radiation research in 2023 to include (i) characterization of low-dose and low-dose-rate radiation risk, (ii) factors to be considered for individualization of radiation risk, (iii) biological mechanisms of low-dose and low-dose-rate radiation effects and (iv) integration of epidemiology and biology. In this context, PLANET established Working Group 2 (Dose and Dose-Rate Mapping for Radiation Risk Studies) to identify the range of doses and dose rates at which observable effects on different endpoints have been reported; Working Group 3 (Species- and Organ-Specific Dose-Rate Effects) to consider the relevance of stem cell dynamics in radiation carcinogenesis of different species and organs; and Working Group 4 (Research Mapping for Radiation-Related Carcinogenesis) to sort out relevant studies, including those on non-mutagenic effects, and to identify priority research areas. These PLANET activities will be used to improve the risk assessment and to contribute to the revision of the next main recommendations of the International Commission on Radiological Protection., Oxford University Press (OUP)
Journal of Radiation Research, 15 Jul. 2024, [Reviewed]

Mechanistic insights into the survival curve of HeLa cells with a short shoulder and their S phase-specific sensitivity
Kenshi Komatsu; Hiroshi Tauchi, Abstract

HeLa cells are a cell line with two unique cellular features: a short-shouldered survival curve and two peaks of radioresistance during the cell cycle phase, while their underlying mechanisms remain unclear. We herein proposed that these radiobiological features are due to a common mechanism by which radiation suppresses homologous recombination repair (HRR) in a dose-dependent manner. This radio-suppression of HRR is mediated by an intra-S checkpoint and reduces survivals of cells in S phase, especially early S phase, resulting in both short shoulder and radioresistance with two peaks in the cell cycle. This new explanation may not be limited to HeLa cells since a similar close association of these features is also observed in other type of cells., Oxford University Press (OUP)
Journal of Radiation Research, 26 Dec. 2023, [Reviewed]

Prediction of late adverse events in pelvic cancer patients receiving definitive radiotherapy using radiation-induced gamma-H2AX foci assay
Masanori Someya; Tomokazu Hasegawa; Asako J Nakamura; Takaaki Tsuchiya; Mio Kitagawa; Toshio Gocho; Sho Mafune; Yutaro Ikeuchi; Hiroshi Tauchi; Koh-ichi Sakata, Abstract

Radiation can induce DNA double-stranded breaks, which are typically detected by the fluorescence of phosphorylated histone H2AX. In this study, we examined the usefulness of the dynamics of radiation-induced gamma-H2AX foci of peripheral blood lymphocytes (PBLs), as a marker of DNA repair ability, in predicting late adverse events from radiotherapy. A total of 46 patients with cervical, vaginal and anal canal cancers treated with radical radiotherapy between 2014 and 2019 were included in this analysis. Concurrent chemotherapy was administered in 36 cases (78.3%). Peripheral blood was obtained before treatment, and then irradiated ex vivo with 1 Gy X-ray. The ratio of radiation-induced gamma-H2AX foci in PBLs measured at 30 min and at 4 h was defined as the foci decay ratio (FDR). With a median follow-up of 54 months, 9 patients (19.6%) were observed to have late genitourinary or gastrointestinal (GU/GI) toxicity. The FDR ranged from 0.51 to 0.74 (median 0.59), with a significantly higher incidence of Grade 1 or higher late adverse events in the FDR ≥ 0.59 group. In multivariate analysis, FDR ≥ 0.59 and hypertension also emerged as significant factors associated with the development of late toxicities. Overall, our results suggest that measurement of radiation-induced gamma-H2AX foci in PBLs may predict the risk of late GU/GI toxicities from chemoradiotherapy, which can enable tailoring the radiation dose to minimize adverse effects., Oxford University Press (OUP)
Journal of Radiation Research, 15 Oct. 2023, [Reviewed]

Dose and dose-rate dependence of DSB-type mutants induced by X-rays or tritium beta-rays: An approach using a hyper-sensitive system
Nagashima H.; Hayashi Y.; Tanimoto S.; Tauchi H., Last, Oxford University Press
Radiation Protection Dosimetry, Sep. 2022, [Reviewed]

NBS1 I171V variant underlies individual differences in chromosomal radiosensitivity within human populations
Tomioka K.; Miyamoto T.; Akutsu S.N.; Yanagihara H.; Fujita K.; Royba E.; Tauchi H.; Yamamoto T.; Koh I.; Hirata E.; Kudo Y.; Kobayashi M.; Okada S.; Matsuura S., Genetic information is protected against a variety of genotoxins including ionizing radiation (IR) through the DNA double-strand break (DSB) repair machinery. Genome-wide association studies and clinical sequencing of cancer patients have suggested that a number of variants in the DNA DSB repair genes might underlie individual differences in chromosomal radiosensitivity within human populations. However, the number of established variants that directly affect radiosensitivity is still limited. In this study, we performed whole-exome sequencing of 29 Japanese ovarian cancer patients and detected the NBS1 I171V variant, which is estimated to exist at a rate of approximately 0.15% in healthy human populations, in one patient. To clarify whether this variant indeed contributes to chromosomal radiosensitivity, we generated NBS1 I171V variant homozygous knock-in HCT116 cells and mice using the CRISPR/Cas9 system. Radiation-induced micronucleus formation and chromosomal aberration frequency were significantly increased in both HCT116 cells and mouse embryonic fibroblasts (MEFs) with knock-in of the NBS1 I171V variant compared with the levels in wild-type cells. These results suggested that the NBS1 I171V variant might be a genetic factor underlying individual differences in chromosomal radiosensitivity., Springer Nature
Scientific Reports, Dec. 2021, [Reviewed]

〔Major achievements〕Induction of somatic mutations by low concentrations of tritiated water (HTO): evidence for the possible existence of a dose-rate threshold
Nagashima; H.; Hayashi; Y.; Sakamoto; Y.; Komatsu; K.; Tauchi; H., Last,
Tritium is a low energy beta emitter and is discharged into the aquatic environment primarily in the form of tritiated water (HTO) from nuclear power plants or from nuclear fuel reprocessing plants. Although the biological effects of HTO exposures at significant doses or dose rates have been extensively studied, there are few reports concerning the biological effects of HTO exposures at very low dose rates. In the present study using a hyper-sensitive assay system, we investigated the dose rate effect of HTO on the induction of mutations. Confluent cell populations were exposed to HTO for a total dose of 0.2 Gy at dose rates between 4.9 mGy/day and 192 mGy/day by incubating cells in medium containing HTO. HTO-induced mutant frequencies and mutation spectra were then investigated. A significant inflection point for both the mutant frequency and mutation spectra was found between 11 mGy/day and 21.6 mGy/day. Mutation spectra analysis revealed that a mechanistic change in the nature of the mutation events occurred around 11 mGy/day. The present observations and published experimental results from oral administrations of HTO to mice suggest that a threshold dose-rate for HTO exposures might exist between 11 mGy/day and 21.6 mGy/day where the nature of the mutation events induced by HTO becomes similar to those seen in spontaneous events., Oxford University Press
Journal of Radiation Research, 24 Apr. 2021, [Reviewed]

Health Effects Triggered by Tritium: How do we get public understanding based on scientifically supported evidence?　　　　　　　　　　　　　　　
Matsumoto; H.; Shimada; Y.; Nakamura; A.J.; Usami; N.; Ojima; M.; Kakinuma; S.; Shimada; M.; Sunaoshi; M.; Hirayama; R.; Tauchi; H., Corresponding, Oxford University Press
Journal of Radiation Research, Apr. 2021, [Reviewed]

Mitotic cells can repair DNA double strand breaks via a homology-directed pathway
Yuki Sakamoto; Tetsuya Kokuta; Ai Teshigahara; Kenta Iijima; Hiroyuki Kitao; Minoru Takata; Hiroshi Tauchi, Last, The choice of repair pathways of DNA double-strand breaks (DSBs) is dependent upon the cell cycle phases. While homologous recombination repair (HRR) is active between the S and G2 phases, its involvement in mitotic DSB repair has not been examined in detail. In the present study, we developed a new reporter assay system to detect homology-directed repair (HDR), a major pathway used for HRR, in combination with an inducible DSB-generation system. As expected, the maximal HDR activity was observed in the late S phase, along with minimal activity in the G1 phase and at the G1/S boundary. Surprisingly, significant HDR activity was observed in M phase, and the repair efficiency was similar to that observed in late S phase. HDR was also confirmed in metaphase cells collected with continuous colcemid exposure. ChIP assays revealed the recruitment of RAD51 to the vicinity of DSBs in M phase. In addition, the ChIP assay for gamma-H2AX and phosphorylated DNA-PKcs indicated that a part of M-phase cells with DSBs could proceed into the next G1 phase. These results provide evidence showing that a portion of mitotic cell DSBs are undoubtedly repaired through action of the HDR repair pathway., Oxford University Press
Journal of Radiation Research, Jan. 2021, [Reviewed]

Discussions on Tritiated Water Treatment for Fukushima Daiichi Nuclear Power Station　　　　　　　　　　　　　　　
Yamanishi; T.; Kakiuchi; H.; Tauchi; H.; Yamamoto; T.; Yamamoto; I
Fusion Science and Technology, Nov. 2020, [Reviewed], [Invited]

放射線感受性の遺伝的個人差を規定する候補素因としてのNBS1遺伝子I171V多型の定量的評価　　　　　　　　　　　　　　　
冨岡 啓太; 藤田 和将; Akutsu Silvia Natsuko; 柳原 啓見; 田内 広; 山本 卓; 小林 正夫; 工藤 美樹; 宮本 達雄; 松浦 伸也, 放射線発がんリスクには、遺伝的個人差があることが示唆されている。本研究では、放射線感受性個人差を規定する新たな遺伝素因の候補遺伝子として、ナイミーヘン染色体不安定症候群の責任遺伝子であるDNA修復遺伝子NBS1のI171V多型に着目した。CRISPR/Cas9システムと1本鎖DNAを用いてNBS1 I171V多型ノックインHCT116(ヒト結腸がん由来)細胞株を樹立し、放射線照射後の微小核形成頻度を評価した。その結果、NBS1 I171V多型は放射線感受性を有意に亢進することが示され、放射線感受性個人差を規定する遺伝素因の一つであることが示唆された。(著者抄録), 広島医学会
広島医学, Apr. 2020

Induction of somatic mutations by low-dose X-rays: The challenge in recognizing radiation-induced events
Haruki Nagashima; Kumiko Shiraishi; Saori Ohkawa; Yuki Sakamoto; Kenshi Komatsu; Shinya Matsuura; Akira Tachibana; Hiroshi Tauchi, It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >
0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >
0.15 Gy. In contrast, mutant frequencies at doses of <
0.1 Gy occurred at non-significant levels. The mutation spectrum in HPRT-deficient mutants revealed that the type of mutations induced by low-dose exposures was similar to that seen in spontaneous mutants. An apparent change in mutation type was observed for mutants induced by doses of >
0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <
0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events., Oxford University Press
Journal of Radiation Research, 01 Apr. 2018, [Reviewed]

Tritium Biology in Japan: A search for a new approach.　　　　　　　　　　　　　　　
Tauchi; H.; Toyoshima-Sasatani; M.; Nagashima; H.; Shimura; T.; Umata; T.; Tachibana; A., Lead
Fusion Engineering and Design, Feb. 2018, [Reviewed], [Invited]

放射線感受性個人差を規定する遺伝素因の定量的評価としてのヒト培養細胞株におけるゲノム編集　　　　　　　　　　　　　　　
宮本達雄; Ekaterina Royba; Silvia Natsuko Akutsu; 細羽康介; 田内広; 山本卓; 工藤美樹; 田代聡; 松浦伸也
広島医学, 2018

Evaluation of ATM heterozygous mutations underlying individual differences in radiosensitivity using genome editing in human cultured cells.
Royba; E.; Miyamoto; T.; Akutsu; S.N.; Hosoba; K.; Tauch; H.; Kudo; Y.; Tashiro; S.; Yamamoto; T.; Matsuura; S., Ionizing radiation (IR) induces DNA double-strand breaks (DSBs), which are an initial step towards chromosomal aberrations and cell death. It has been suggested that there are individual differences in radiosensitivity within human populations, and that the variations in DNA repair genes might determine this heterogeneity. However, it is difficult to quantify the effect of genetic variants on the individual differences in radiosensitivity, since confounding factors such as smoking and the diverse genetic backgrounds within human populations affect radiosensitivity. To precisely quantify the effect of a genetic variation on radiosensitivity, we here used the CRISPR-ObLiGaRe (Obligate Ligation-Gated Recombination) method combined with the CRISPR/Cas9 system and a nonhomologous end joining (NHEJ)-mediated knock-in technique in human cultured cells with a uniform genetic background. We generated ATM heterozygous knock-out (ATM(+/-)) cell clones as a carrier model of a radiation-hypersensitive autosomal-recessive disorder, ataxia-telangiectasia (A-T). Cytokinesis-blocked micronucleus assay and chromosome aberration assay showed that the radiosensitivity of ATM(+/-)cell clones was significantly higher than that of ATM(+/+) cells, suggesting that ATM gene variants are indeed involved in determining individual radiosensitivity. Importantly, the differences in radiosensitivity among the same genotype clones were small, unlike the individual differences in fibroblasts derived from A-T-affected family members., NATURE PUBLISHING GROUP
Scientific Reports, 2017, [Reviewed]

Mutations in the FHA-domain of ectopically expressed NBS1 lead to radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination
Ohara; M.; Funyu; Y.; Ebara; S.; Sakamoto; Y.; Seki; R.; Iijima; K.; Ohishi; A.; Kobayashi; J.; Komatsu; K.; Tachibana; A.; Tauchi; H., Last, Ionizing radiation induces DNA double-strand breaks (DSBs). Mammalian cells repair DSBs through multiple pathways, and the repair pathway that is utilized may affect cellular radiation sensitivity. In this study, we examined effects on cellular radiosensitivity resulting from functional alterations in homologous recombination (HR). HR was inhibited by overexpression of the forkhead-associated (FHA) domain-mutated NBS1 (G27D/R28D: FHA-2D) protein in HeLa cells or in hamster cells carrying a human X-chromosome. Cells expressing FHA-2D presented partially (but significantly) HR-deficient phenotypes, which were assayed by the reduction of gene conversion frequencies measured with a reporter assay, a decrease in radiation-induced Mre11 foci formation, and hypersensitivity to camptothecin treatments. Interestingly, ectopic expression of FHA-2D did not increase the frequency of radiation-induced somatic mutations at the HPRT locus, suggesting that a partial reduction of HR efficiency has only a slight effect on genomic stability. The expression of FHA-2D rendered the exponentially growing cell population slightly (but significantly) more sensitive to ionizing radiation. This radiosensitization effect due to the expression of FHA-2D was enhanced when the cells were irradiated with split doses delivered at 24-h intervals. Furthermore, enhancement of radiation sensitivity by split dose irradiation was not seen in contact-inhibitedG0/G1 populations, even though the cells expressed FHA-2D. These results suggest that the FHA domain of NBS1 might be an effective molecular target that can be used to induce radiosensitization using low molecular weight chemicals, and that partial inhibition of HR might improve the effectiveness of cancer radiotherapy., OXFORD UNIV PRESS
Journal of Radiation Research, Mar. 2014, [Reviewed]

Histone chaperone FACT regulates homologous recombination by chromatin remodeling through interaction with RNF20.
Oliveira; D.V.; Kato; A.; Nakamura; K.; Ikura; T.; Okada; M.; Kobayashi; J.; Yanagihara; H.; Saito; Y.; Tauchi; H.; Komatsu; K., The E3 ubiquitin ligase RNF20 regulates chromatin structure through ubiquitylation of histone H2B, so that early homologous recombination repair (HRR) proteins can access the DNA in eukaryotes during repair. However, it remains unresolved how RNF20 itself approaches the DNA in the presence of chromatin structure. Here, we identified the histone chaperone FACT as a key protein in the early steps of HRR. Depletion of SUPT16H, a component of FACT, caused pronounced defects in accumulations of repair proteins and, consequently, decreased HRR activity. This led to enhanced sensitivity to ionizing radiation (IR) and mitomycin-C in a fashion similar to RNF20-deficient cells, indicating that SUPT16H is essential for RNF20-mediated pathway. Indeed, SUPT16H directly bound to RNF20 in vivo, and mutation at the RING-finger domain in RNF20 abolished its interaction and accumulation, as well as that of RAD51 and BRCA1, at sites of DNA double-strand breaks (DSBs), whereas the localization of SUPT16H remained intact. Interestingly, PAF1, which has been implicated in transcription as a mediator of FACT and RNF20 association, was dispensable for DNA-damage-induced interaction of RNF20 with SUPT16H. Furthermore, depletion of SUPT16H caused pronounced defects in RNF20-mediated H2B ubiquitylation and thereby, impaired accumulation of the chromatin remodeling factor SNF2h. Consistent with this observation, the defective phenotypes of SUPT16H were effectively counteracted by enforced nucleosome relaxation. Taken together, our results indicate a primary role of FACT in RNF20 recruitment and the resulting chromatin remodeling for initiation of HRR., COMPANY OF BIOLOGISTS LTD
Journal of Cell Science, 2014, [Reviewed]

The combination of hyperthermia or chemotherapy with Gimeracil for effective radiosensitization.
Takagi; M.; Sakata; K.; Someya; M.; Matsumoto; Y.; Tauchi; H.; Hareyama; M.; Fukusima; M., Purpose. 5-chloro-2,4-dihydroxypyridine (gimeracil) is a component of the oral fluoropyrimidine derivative S-1. Gimeracil was originally added to S-1 to yield prolonged 5-fluorouracil (5-FU) concentrations in serum and tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We previously demonstrated that gimeracil enhances the efficacy of radiotherapy through the suppression of homologous recombination (HR) in DNA double strand repair. The goal of this paper was to examine the effects of gimeracil on the sensitivity of anticancer drugs and hyperthermia in order to obtain effective radiosensitization.
Materials and methods. Various cell lines, including DLD 1 (human colon carcinoma cells) and cells deficient in HR or nonhomologous end-joining (NHEJ), were used in clonogenic assays. The survival of these cells after various treatments (e.g., drug treatment, heat treatment, and radiation) was determined based on their colony-forming ability.
Results. Gimeracil enhanced cell-killing effects of camptothecin (CPT), 5-FU, and hydroxyurea. Gimeracil sensitized effects of CPT or 5-FU to cells deficient in HR or NHEJ to a similar extent as in other cells (DLD1 and a parent cell), indicating that its sensitizing mechanisms may be different from inhibition of HR or NHEJ. Combination of gimeracil and CPT or 5-FU sensitized radiation more effectively than each modality alone. Gimeracil also enhanced heat sensitivity at 42 degrees C or more. The degree of heat sensitization with gimeracil increased as the temperature increased, and the combination of gimeracil and heat-sensitized radiation was more effective than each modality alone.
Conclusion. Gimeracil enhanced sensitivity of CPT, 5-FU, and hyperthermia. Combination of these modalities sensitized radiation more efficiently than each modality alone., URBAN & VOGEL
Strahlentherapie und Onkologie, 2012, [Reviewed]

Yield of single-, double-strand breaks and nucleobase lesions in fully hydrated plasmid DNA films irradiated with high-LET charged particles.
Ushigome; T.; Shikazono; N.; Fujii; K.; Watanabe; R.; Suzuki; M.; Takakura; C.; Tauchi; H.; Yokoya A., We measured the yield and spectrum of strand breaks and nucleobase lesions produced in fully hydrated plasmid DNA films to determine the linear energy transfer (LET) dependence of DNA damage induced by ion-beam irradiation in relation to the change in the atomic number of ions. The yield of isolated damage was revealed as a decrease in prompt SSBs with increasing LET of He2+, C5+6+ and Ne-8+,Ne-10+ ions. On the other hand, the yields of prompt DSBs increased with increasing ion LET. SSBs were additionally induced in ion-irradiated DNA film by treatment with two kinds of base excision repair proteins (glycosylases), Nth and Fpg, indicating that base lesions are produced in the hydrated DNA film. This result shows that nucleobase lesions are produced via both chemical reactions with diffusible water radicals, such as OH radicals, and direct energy deposition onto DNA and the hydrated water layer. Nth-sensitive sites deduced to be pyrimidine lesions, such as 5,6-dihydrothymine (DHT), showed a relatively larger yield than Fpg-sensitive sites deduced to be purine lesions, such as 7,8-dihydro-8-oxo-2'deoxyguanine (8-oxoGua), for all ion exposures tested. The yield of SSBs or DSBs observed by enzyme treatment decreased noticeably with increasing LET for all tested ions. These results indicated that higher-LET ions preferentially produce a complex type of damage that might compromise the activities of the glycosylases used in this study. These findings are biologically important since, under cell mimicking conditions, persistent DNA damage occurs in part due to direct energy deposition on the DNA or hydrated water shell that is specifically induced by dense ionization in the track. (C) 2012 by Radiation Research Society, RADIATION RESEARCH SOC
Radiation Research, 2012, [Reviewed]

Effects of depletion of dihydropyrimidine dehydrogenase on focus formation and RPA phosphorylation.
Someya; M; Sakata; K.; Matsumoto; Y.; Tauchi; H.; Kai; M.; Hareyama; M.; Fukushima; M., Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase (DPYD), partially inhibits homologous recombination (HR) repair and has a radiosensitizing effect as well as enhanced sensitivity to Camptothecin (CPT). DPYD is the target protein for radiosensitization by Gimeracil. We investigated the mechanisms of sensitization of radiation and CPT by DPYD inhibition using DLD-1 cells treated with siRNA for DPYD. We investigated the focus formation of various kinds of proteins involved in HR and examined the phosphorylation of RPA by irradiation using Western blot analysis. DPYD depletion by siRNA significantly restrained the formation of radiation-induced foci of Rad51 and RPA, whereas it increased the number of foci of NBS1. The numbers of colocalization of NBS1 and RPA foci in DPYD-depleted cells after radiation were significantly smaller than in the control cells. These results suggest that DPYD depletion is attributable to decreased single-stranded DNA generated by the Mre11/Rad50/NBS1 complex-dependent resection of DNA double-strand break ends. The phosphorylation of RPA by irradiation was partially suppressed in DPYD-depleted cells, suggesting that DPYD depletion may partially inhibit DNA repair with HR by suppressing phosphorylation of RPA. DPYD depletion showed a radiosensitizing effect as well as enhanced sensitivity to CPT. The radiosensitizing effect of DPYD depletion plus CPT was the additive effect of DPYD depletion and CPT. DPYD depletion did not have a cell-killing effect, suggesting that DPYD depletion may not be so toxic. Considering these results, the combination of CPT and drugs that inhibit DPYD may prove useful for radiotherapy as a method of radiosensitization., OXFORD UNIV PRESS
Journal of Radiation Research, 2012, [Reviewed]

Regulation of homologous recombination by RNF20-dependent H2B ubiquitination
Nakamura; K.; Kato; A.; Kobayashi; J.; Yanagihara; H.; Sakamoto; S.; Oliveira; D. V.N.P.; Shimada; M.; Tauchi; H.; 他4名, The E3 ubiquitin ligase RNF20 regulates chromatin structure by monoubiquitinating histone H2B in transcription. Here, we show that RNF20 is localized to double-stranded DNA breaks (DSBs) independently of H2AX and is required for the DSB-induced H2B ubiquitination. In addition, RNF20 is required for the methylation of H3K4 at DSBs and the recruitment of the chromatin-remodeling factor SNF2h. Depletion of RNF20, depletion of SNF2h, or expression of the H2B mutant lacking the ubiquitination site (K120R) compromises resection of DNA ends and recruitment of RAD51 and BRCA1. Consequently, cells lacking RNF20 or SNF2h and cells expressing H2B K120R exhibit pronounced defects in homologous recombination repair (HRR) and enhanced sensitivity to radiation. Finally, the function of RNF20 in HRR can be partially bypassed by forced chromatin relaxation. Thus, the RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling., CELL PRESS
Molecular Cell, 05 Mar. 2011, [Reviewed]

H2B Ubiquitination-mediated chromatin remodeling in response to double-stranded DNA breaks in vertebrates　　　　　　　　　　　　　　　
Kenshi Komatsu; Kyosuke Nakamura; Akihiro Kato; Junya Kobayashi; Hiromi Yanagihara; Shuichi Sakamoto; Douglas V.N.P. Oliveira; Mikio Shimada; Satoshi Tashiro; Hiroshi Tauchi
日本分子生物学会，パシフイコ横浜,2011 年12 月15 日（招待講演）, 2011, [Reviewed]

The Induction of Radioadaptive Response by 3H-Thymidine in Mouse Fibroblast Cells.　　　　　　　　　　　　　　　
Tachibana, A; Ito, K; Fujii, N; Saotome, S; Tauchi, H
Fusion Science and Technology, 2011, [Reviewed]

Assessment of biological effect of tritiated water by using hypersensitive system.
Tauchi; H.; Imamura; H.; Inoue; M.; Komatsu; K.; Tachibana; A, Lead, An exposure of human or animals to tritium radiation from nuclear fusion reactor is expected to be a low dose and with low dose-rate. We are focusing on the biological effects of tritiated water (HTO) given at low dose and/or with low dose rate. Hypersensitive assay systems for radiation biological experiments using cultured mammalian cells or transgenic mice have been established and their availability for assessment of biological effects of HTO were tested. A hypersensitive detection system for mutagenesis at Hprt locus was established by using hamster cells carrying a human X-chromosome. The cells present more than 50-fold sensitivity for Hprt-deficient mutation, and this allowed us to detect a significant elevation of mutation frequency by radiations at the dose of less than 0.2 Gy.
Because the reverse dose rate effect has been reported for mutation induction by high LET radiation such as neutrons, we first tested whether the reverse dose rate effects could be seen for HTO (tritium beta-rays) or not. No significant change in mutation frequency by HTO was observed in the range of dose rates between 0.05 cGy/h and 2.0 cGy/h, whereas clear reverse dose rate effects was observed in the case of fission neutrons or carbon beam. The result suggests that the reverse dose rate effect does not apply in the case of mutation induction by HTO. In addition, mutation spectrum in the mutants induced by HTO was similar to those in spontaneously induced mutants, suggesting that exposure to a certain level of HTO could enhance the spontaneous mutagenesis., AMER NUCLEAR SOC
Fusion Science and Technology, 2011, [Reviewed], [Invited]

Gimeracil, an inhibitor of dihydropyrimidine dehydrogenase, inhibits the early step in homologous recombination.
Sakata; K.; Someya; M.; Matsumoto; Y.; Tauchi; H.; Kai; M.; Toyota; M.; Takagi; M.; Hareyama; M.; Fukushima; M., Gimeracil (5-chloro-2, 4-dihydroxypyridine) is an inhibitor of dihydropyrimidine dehydrogenase (DPYD), which degrades pyrimidine including 5-fluorouracil in the blood. Gimeracil was originally added to an oral fluoropyrimidine derivative S-1 to yield prolonged 5-fluorouracil concentrations in serum and tumor tissues. We have already reported that gimeracil had radiosensitizing effects by partially inhibiting homologous recombination (HR) in the repair of DNA double strand breaks. We investigated the mechanisms of gimeracil radiosensitization. Comet assay and radiation-induced focus formation of various kinds of proteins involved in HR was carried out. siRNA for DPYD were transfected to HeLa cells to investigate the target protein for radiosensitization with gimeracil. SCneo assay was carried out to examine whether DPYD depletion by siRNA inhibited HR repair of DNA double strand breaks. Tail moments in neutral comet assay increased in gimeracil-treated cells. Gimeracil restrained the formation of foci of Rad51 and replication protein A (RPA), whereas it increased the number of foci of Nbs1, Mre11, Rad50, and FancD2. When HeLa cells were transfected with the DPYD siRNA before irradiation, the cells became more radiosensitive. The degree of radiosensitization by transfection of DPYD siRNA was similar to that of gimeracil. Gimeracil did not sensitize DPYD-depleted cells. Depletion of DPYD by siRNA significantly reduced the frequency of neopositive clones in SCneo assay. Gimeracil partially inhibits the early step in HR. It was found that DPYD is the target protein for radiosensitization by gimeracil. The inhibitors of DPYD, such as gimeracil, could enhance the efficacy of radiotherapy through partial suppression of HR-mediated DNA repair. (Cancer Sci 2011; 102: 1712-1716), WILEY-BLACKWELL
Cancer Science, 2011, [Reviewed]

NBS1 recruits RAD18 via a RAD6-like motif and regulates Pol -dependent translesion DNA synthesis.
Yanagihara; H.; Kobayashi; J.; Tateishi; S.; Kato; A.; Matsuura; S.; Tauchi; H.; Yamada; K.; Takezawa; J.; Sugasawa; K.; Masutani; C.; Hanaoka; F.; Weemaes; C. M.; Mori; T.; Zou; L.; Komatsu; K., Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6 and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are regulated by DNA damage is not fully understood. We show that NBS1 (mutated in Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the recruitment of RAD18 to sites of DNA damage. Disruption of NBS1 abolished RAD18-dependent PCNA ubiquitination and Polη focus formation, leading to elevated UV sensitivity and mutation. Unexpectedly, the RAD18-interacting domain of NBS1, which was mapped to its C terminus, shares structural and functional similarity with the RAD18-interacting domain of RAD6. These domains of NBS1 and RAD6 allow the two proteins to interact with RAD18 homodimers simultaneously and are crucial for Polη-dependent UV tolerance. Thus, in addition to chromosomal break repair, NBS1 plays a key role in translesion DNA synthesis.
Molecular Cell, 2011, [Reviewed]

Gimeracil sensitizes cells to radiation via inhibition of homologous recombination.
Takagi; M.; Sakata; K.; Someya; M.; Tauchi; H.; Iijima; K.; Matsumoto; Y.; Torigoe; T.; Takahashi; A.; Hareyama; M.; Fukushima; M., Background and purpose. 5-Chloro-2,4-dihydroxypyridine (Gimeracil) is a component of an oral fluoro-pyrimidine derivative S-1 Gimeracil is originally added to S-1 to yield prolonged 5-FU concentrations in tumor tissues by inhibiting dihydropyrimidine dehydrogenase, which degrades 5-FU. We found that Gimeracil by itself had the radiosensitizing effect
Methods and materials We used various cell lines deficient in non-homologous end-joining (NHEJ) or homologous recombination (HR) as well as DLD-1 and HeLa in clonogenic assay gamma-H2AX focus formation and SCneo assay was performed to examine the effects of Gimeracil on DNA double strand bleak (DSB) repair mechanisms
Results Results of gamma-H2AX focus assay indicated that Gimeracil inhibited DNA DSB repair It did not sensitize cells deficient in HR but sensitized those deficient in NHEJ In SCneo assay, Gimeracil reduced the frequency of neo-positive clones Additionally, it sensitized the cells in S-phase more than in G0/G1
Conclusions Gimeracil inhibits HR. Because HR plays key roles in the repair of DSBH caused by radiotherapy, Gimeracil may enhance the efficacy of radiotherapy through the suppression of HR-mediated DNA repair pathways (C) 2010 Elsevier Ireland Ltd. All rights reserved Radiotherapy and Oncology 96 (2010) 259-266, ELSEVIER IRELAND LTD
Radiotherapy and Oncology, 2010, [Reviewed]

DNA修復応答とゲノム不安定性 ヒストンH2Bユビキチン化による相同組換え修復の制御(DNA damage and cancer Control of homologous recombination by H2B ubiquitination)　　　　　　　　　　　　　　　
小松 賢志; 加藤 晃弘; 小林 純也; 田内 広; 田代 聡, 日本癌学会
日本癌学会総会記事, Aug. 2009

Corrigendum to "Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1" [Biochem. Biophys. Res. Commun. 380 (2009) 752-757] (DOI:10.1016/j.bbrc.2009.01.109)
J. Kobayashi; H. Tauchi; B. Chen; S. Burma; S. Tashiro; S. Matsuura; K. Tanimoto; D.J. Chen; K. Komatsu
Biochemical and Biophysical Research Communications, 2009, [Reviewed]

Two major factors involved in the reverse dose-rate effect for somatic mutation induction are the cell cycle position and LET value
Tauchi; H.; Waku; H.; Matumoto; E.; Yara; S.; Okumura; S.; Iwata; Y.; Komatsu; K.; Frusawa; Y.; Eguchi-Kasai; K.; Tachibana; A., Lead, To study mechanisms which could be involved in the reverse dose rate effect observed during mutation induction after exposure to high LET radiation, synchronized mouse L5178Y cells were exposed to carbon 290 MeV/n beams with different LET values at the G2/M, G1, G1/S or S phases in the cell cycle. The frequency of Hprt-deficient (6-thioguanine-resistant) mutant induction was subsequently determined. The results showed that after exposure to high LET value radiation (50.8 and 76.5 keW/mu m), maximum mutation frequencies were seen at the G2/M phase, but after exposure to lower LET radiation (13.3 keV/mu m), the highest mutation frequencies were observed at the G1 phase. The higher LET beam always produced higher mutation frequencies in the G2/M phase than in the G1 phase, regardless of radiation dose. These results suggest that cells in the G2/M phase is hyper-sensitive for mutation induction from high LET radiation, but not to mutation induction from low LET radiation. Molecular analysis of mutation spectra showed that large deletions (which could include almost entire exons) of the mouse Hprt gene were most efficiently induced in G2/M cells irradiated with high LET radiation. These entire exon deletions were not as frequent in cells exposed to lower LET radiation. This suggests that inappropriate recombination repair might have occurred in response to condensed damage in condensed chromatin in the G2/M phase. In addition, by using a hyper-sensitive mutation detection system (GM06318-10 cells), a reverse dose-rate effect was clearly observed after exposure to carbon beams with higher LET values (66 keV/mu m), but not after exposure to beams with lower LET values (13.3 keV/mu m). Thus, G2/M sensitivity towards mutation induction, and the dependence on radiation LET values could both be major factors involved in the reverse dose rate effect produced by high LET radiation., JAPAN RADIATION RESEARCH SOC
Journal of Radiation Research, 2009, [Reviewed]

Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1
Kobayashi; J.; Tauchi; H.; Chen; B.; Bruma; S.; Tashiro; S.; Matsuura; S.; Tanimoto; K.; Chen; D. J.; Komatsu; K., Phosphorylated histone H2AX (gamma-H2AX) functions in the recruitment of DNA damage response Proteins to DNA double-strand breaks (DSBs) and facilitates DSB repair. ATM also co-localizes with gamma-H2AX at DSB sites following its auto-phosphorylation. However, it is unclear whether gamma-H2AX has a role in activation of ATM-dependent cell cycle checkpoints. Here, we show that ATM as well as NBS1 is recruited to damaged-chromatin in a gamma-H2AX-dependent manner. Foci formation of phosphorylated ATM and ATM-dependent phosphorylation is repressed in H2AX-knockdown cells. Furthermore, anti-gamma-H2AX antibody co-immunoprecipitates an ATM-Iike protein kinase activity in vitro and recombinant H2AX increases in vitro kinase activity of ATM from un-irradiated cells. Moreover, H2AX-deficient cells exhibited a defect in ATM-dependent cell cycle checkpoints. Taken together, gamma-H2AX has important role for effective DSB-dependent activation of ATM-related damage responses via NBS1. (C) 2009 Elsevier Inc. All rights reserved., ACADEMIC PRESS INC ELSEVIER SCIENCE
Biochemical and Biophysical Research Communications, 2009, [Reviewed]

Homologous recombination but not nucleotide excision repair plays a pivotal role in tolerance to DNA-protein crosslinks in mammalian cells
Nakano; T.; Katafuchi; A.; Matsubara; M.; Terato; H.; Tsuboi; T.; Masuda; T.; Tatsumoto; M.; Pack; S.-P. Makino; K.; Croteau; D. L.; Van Houten; B.; Iijima; K.; Tauchi; H.; Ide; H, DNA-protein cross-links (DPCs) are unique among DNA lesions in their unusually bulky nature. The steric hindrance imposed by cross-linked proteins (CLPs) will hamper DNA transactions, such as replication and transcription, posing an enormous threat to cells. In bacteria, DPCs with small CLPs are eliminated by nucleotide excision repair (NER), whereas oversized DPCs are processed exclusively by RecBCD-dependent homologous recombination (HR). Here we have assessed the roles of NER and HR for DPCs in mammalian cells. We show that the upper size limit of CLPs amenable to mammalian NER is relatively small (8-10 kDa) so that NER cannot participate in the repair of chromosomal DPCs in mammalian cells. Moreover, CLPs are not polyubiquitinated and hence are not subjected to proteasomal degradation prior to NER. In contrast, HR constitutes the major pathway in tolerance of DPCs as judged from cell survival and RAD51 and gamma-H2AX nuclear foci formation. Induction of DPCs results in the accumulation of DNA double strand breaks in HR-deficient but not HR-proficient cells, suggesting that fork breakage at the DPC site initiates HR and reactivates the stalled fork. DPCs activate both ATR and ATM damage response pathways, but there is a time lag between two responses. These results highlight the differential involvement of NER in the repair of DPCs in bacterial and mammalian cells and demonstrate the versatile and conserved role of HR in tolerance of DPCs among species., AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Journal of Biological Chemistry, 2009, [Reviewed]

Rapid myeloid recovery as a possible mechanism of whole-body radioadaptive response
Ohtsuka; K.; Koana; T.; Tomita; M.; Ogata; H.; Tauchi; H., We investigated the mechanism underlying the radioadaptive response that rescues mice from hematopoietic failure. C57BL/6 mice were irradiated with low-dose acute X rays (0.5 Gy) for priming 2 weeks; prior to a high-dose (6 Gy) challenge irradiation. Bone marrow cells, erythrocytes and platelets in low-dose-preirradiated mice showed earlier recovery after the challenge irradiation than those in mice subjected only to the challenge irradiation. This suggests that hematopoiesis is enhanced after a challenge irradiation in preirradiated mice. The rapid recovery of bone marrow cells after the challenge irradiation was consistent with the proliferation of hematopoietic progenitors expressing the cell surface markers Lin(-), Sca-1(-) and c-Kit(+) in low-dose-preirradiated mice. A subpopulation of myeloid (Mac-1(+)/Gr-1(+)) cells, which were descendants of Lin(-), Sca-1(-) and c-Kit(+) cells, rapidly recovered in the bone marrow oflow-dose-preirradiated mice, whereas the number of B-lymphoid (CD19(+)/B220(+)) cells did not show a statistically significant increase. Plasma cytokine profiles were analyzed using antibody arrays, and results indicated that the concentrations of several growth factors for myelopoiesis after the challenge irradiation were considerably increased by low-dose preirradiation. The rapid recovery of erythrocytes and platelets but not leukocytes was observed in the peripheral blood of preirradiated mice, suggesting that low-dose preirradiation triggered the differentiation to myelopoiesis. Thus the adaptive response induced by low-dose preirradiation in terms of the recovery kinetics of the number of hematopoietic cells may be due to the rapid recovery of the number of myeloid cells after high-dose irradiation. (c) 2008 by Radiation Research Society., RADIATION RESEARCH SOC
Radiation Research, Sep. 2008, [Reviewed]

NBS1 Prevents Chromatid-Type Aberrations through ATM-Dependent Interactions with SMC1
Antoccia; A.; Sakamoto; S.; Matsuura; S.; Tauchi; H.; Komatsu; K., Nijmegen breakage syndrome shares several common cellular features with ataxia telangiectasia, including chromosomal instability and aberrant S- and G(2)-phase checkpoint regulation. We show here that after irradiation, NBS1 interacts physically with both BRCA1 and SMC1, a component of the cohesin complex, and that their interactions are completely abolished in AT cells. It is noted that BRCA1 is required for the interaction of NBS1 with SMC1, whereas the reverse is not the case, since BRCA1 is able to bind to NBS1 in the absence of an NBS1/SMC1 interaction as observed in MRE11- or RAD50-deficient cells. This indicates that ATM and BRCA1 are upstream of the NBS1/SMC1 interaction. Furthermore, the interaction of NBS1 with SMC1 requires both conserved domains of NBS in the N-terminus and the C-terminus, since they are indispensable for binding of NBS1 to BRCA1 and to MRE11/ATM, respectively. The interaction of NBS1 with SMC1 and the resulting phosphorylation are compromised in the clones lacking either the N- or C-terminus of NBS1, and as a consequence, chromatid-type aberrations are enhanced after irradiation. Our results reveal that ATM plays a fundamental role in promoting the radiation-induced interaction of NBS1 with SMC1 in the presence of BRCA1, leading to the maintenance of chromosomal integrity. (c) 2008 by Radiation Research Society., RADIATION RESEARCH SOC
Radiation Research, Sep. 2008, [Reviewed]

NBS1 regulates a novel apoptotic pathway through Bax activation
Iijima; K.; Muranaka; C.; Kobayashi; J.; Sakamoto; S.; Komatsu; K.; Matsuura; S.; Kubota; N.; Tauchi; H., Corresponding, DNA damage induced apoptosis, along with precise DNA damage repair, is a critical cellular function, and both of these functions are necessary for cancer prevention. The NBS1 protein is known to be a key regulator of DNA damage repair. It acts by forming a complex with Rad50/Mre11 and by activating ATM. We show here that NBS1 regulates a novel p53 independent apoptotic pathway in response to DNA damage. DNA damage induced apoptosis was significantly reduced in NBS1 deficient cells regardless of their p53 status. Experiments using a series of cell lines expressing mutant NBS1 proteins revealed that NBS1 is able to regulate the activation of Bax and Caspase-3 without the FHA, Mre11-binding, or the ATM-interacting domains, whereas the phosphorylation sites of NBS1 were essential for Bax activation. Expression of apoptosis-related transcription factors such as E2F1 and their downstream pro-apoptotic factors were not related to this apoptosis induction. Interestingly, NBS1 regulates a novel Bax activation pathway by disrupting the Ku70-Bax complex which is required for activation of the mitochondrial apoptotic pathway. This dissociation of the Ku70-Bax complex can be mediated by acetylation of Ku70, and NBS1 can function in this process through a protein-protein interaction with Ku70. Thus, NBS1 is a key protein involved in the prevention of carcinogenesis, not only through the precise repair of damaged DNA by homologous recombination (HR) but also by its role in the elimination of inappropriately repaired cells. (c) 2008 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
DNA Repair, 2008, [Reviewed]

「Functional interaction between histone H2A χ and NBS1 on ATM-dependent DNA damage response. 」　　　　　　　　　　　　　　　
Kobayashi J; Tauchi H; Matsuura S; Chen DJ; Komatsu K
13th International Congress of Radiation Research 2007 年7 月 San Francisco, 2007, [Reviewed]

Human NBS1 and MRE11 associate for regulation of checkpoints and for homologous recombination repair.
K. Komatsu; A. Antoccia; S. Sakamoto; J. Kobayashi; S.Matsuura; H. Tauchi
International Congress Series 1299:158-163, ELSEVIER, Amsterdam., 2007, [Reviewed]

NBS1 and MRE11 associate for responses to DNA double-strand breaks
K. Komatsu; A. Antoccia; S. Sakamoto; J. Kobayashi; S. Matsuura; H. Tauchi
International Congress Series, 2007, [Reviewed]

Characterization of the plant homolog of Nijmegen breakage syndrome 1: involvement in DNA repair and recombination.　　　　　　　　　　　　　　　
Noriyuki Akutsu; Kenta Iijima; Takeo Hinata; Hiroshi Tauchi, Corresponding
Biochemical and Biophysical Research Communications, Jan. 2007, [Reviewed]

Homologous recombination repair is regulated by domains at the N- and C-terminus of NBS1 and is dissociated with ATM functions
Sakamoto; S.; Iijima; K.; Mochizuki; D.; Nakamura; K.; Teshigawara; K.; Kobayashi; J.; Matsuura; S.; Tauchi; H.; Komatsu; K., Corresponding, The proteins responsible for radiation sensitive disorders, NBS1, kinase ataxia- telangiectasia-( A- T)- mutated ( ATM) and MRE11, interact through the C- terminus of NBS1 in response to the generation of DNA double- strand breaks ( DSBs) and are all implicated in checkpoint regulation and DSB repair, such as homologous recombination ( HR). We measured the ability of several NBS1 mutant clones and A- T cells to regulate HR repair using the DR- GFP or SCneo systems. ATM deficiency did not reduce the HR repair frequency of an induced DSB, and it was confirmed by findings that HR frequencies are only slightly affected by deletion of ATM- binding site at the extreme C-terminus of NBS1. In contrast, The HR- regulating ability is dramatically reduced by deletion of the MRE11- binding domain at the C- terminus of NBS1 and markedly inhibited by mutations in the FHA/ BRCT domains at the N- terminus. This impaired capability in HR is consistent with a failure to observe MRE11 foci formation. Furthermore, normal HR using sister chromatid was completely inhibited by the absence of FHA/ BRCT domains. These results suggested that the N- and C- terminal domains of NBS1 are the major regulatory domains for HR pathways, very likely through the recruitment and retention of the MRE11 nuclease to DSB sites in an ATM-independent fashion., NATURE PUBLISHING GROUP
Oncogene, 2007, [Reviewed]

TopBP1 associates with NBS1 and is involved in homologous recombination repair
Morishima; K.; Sakamoto; S.; Kobayashi; J; Izumi; H.; Suda; T.; Matsumoto; Y.; Tauchi; H.; Ide; H.; Komatsu; K.; Matsuura; S, TopBP1 is involved in DNA replication and DNA damage checkpoint. Recent studies have demonstrated that TopBP1 is a direct positive effecter of ATR. However, it is not known how TopBP1 recognizes damaged DNA. Here, we show that TopBP1 formed nuclear foci after exposure to ionizing radiation, but such TopBP1 foci were abolished in Nijmegen breakage syndrome cells. We also show that TopBP1 physically associated with NBS1 in vivo. These results suggested that NBS1 might regulate TopBP1 recruitment to the sites of DNA damage. TopBP1-depleted cells showed hypersensitivity to Mitomycin C and ionizing radiation, an increased frequency of sister-chromatid exchange level, and a reduced frequency of DNA double-strand break induced homologous recombination repair. Together, these results suggested that TopBP1 might be a mediator of DNA damage signaling from NBS1 to ATR and promote homologous recombination repair. (c) 2007 Elsevier Inc. All rights reserved., ACADEMIC PRESS INC ELSEVIER SCIENCE
Biochemical and Biophysical Research Communications, 2007, [Reviewed]

Association of DNA-PK activity and radiation-induced NBS1 foci formation in lymphocytes with clinical malignancy in breast cancer patients
Someya; M.; Sakata; K.; Matsumoto; Y.; Tauchi; H.; Narimatsu; H.; Hareyama; M., DNA double-strand break (DSB) is one of the most deleterious lesions induced by DNA damaging agents. DSB repair pathway is implicated in maintaining genomic integrity via suppression of genetic instability and neoplastic transformation. DNA-dependent protein kinase (DNA-PK) has a pivotal role in DNA DSB repair. The Nijmegen breakage syndrome protein (NBS1), essential for DSB repair, re-localizes into subnuclear structures upon induction of DNA damage by ionizing radiation, forming so-called ionizing radiation-induced foci (IRIF), which is visualized by immunostaining. We measured DNA-PK activity and the number of persistent NBS1 IRIF per nucleus 24 h after irradiation of peripheral blood lymphocytes (PBL) from patients with sporadic breast cancer. Chromosomal aberrations were examined by cytogenetic methods. We examined the relationship between these measurements and clinical characteristics of patients such as tumor size, lymph node metastasis and nuclear grade of cancer cells. A higher number of NBS1 IRIF or lower DNA-PK activity correlated with higher chromosome instability. Patients whose PBL had lower DNA-PK or higher NBS1 IRIF had aggressive cancer phenotypes such as a larger tumor, higher nuclear grade and positive axillary lymph node metastasis. The combination of DNA-PK activity and NBS1 IRIF were useful for predicting lymph node metastasis. The ability of DSB repair in PBL is related to aggressive breast cancer phenotypes. Axillary lymph node dissection can be avoided by examining DNA-PK activity and NBS1 IRIF of PBL, which can contribute to improving the quality of life of breast cancer patients., PROFESSOR D A SPANDIDOS
Oncology Report, 2007, [Reviewed]

NBS1 regulates DNA-damage induced apoptosis independent of p53.　　　　　　　　　　　　　　　
H. Tauchi; K. Iijima; C. Muranaka; J. Kobayashi; K. Komatsu; S. Matsuura; Y. Ichimasa
20th IUBMB International Congress of Biochemistry and molecular Biology and 11th FAOBMB Congress. Kyoto, Japan., 2006, [Reviewed]

Nijmegen breakage syndrome and functions of the responsible protein, NBS1.
A. Antoccia; J. Kobayashi; H. Tauchi; S. Matsuura; K. Komatsu
Genome dynamics, 2006, [Reviewed]

BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome
) Matsuura; S.; Matsumoto; Y.; Morishima; K.; Izumi; H.; Matsumoto; H.; Ito; E.; Tsutsui; K.; Kobayashi; J.; Tauchi; H.; Kajiwara; K.; Hama; S.; Kurisu; K.; Tahara; H.; Oshimura; M.; Komatsu; K.; Ikeuchi; T.; Kajii; T., Cancer-prone syndrome of premature chromatid separation (PCS syndrome) with mosaic variegated aneuploidy (MVA) is a rare autosomal recessive disorder characterized by growth retardation, microcephaly, childhood cancer, premature chromatid separation of all chromosomes, and mosaicism for various trisomies and monosomies. Biallelic BUB1B mutations were recently reported in five of eight families with MVA syndrome (probably identical to the PCS syndrome). We here describe molecular analysis of BUB1B (encoding BubR1) in seven Japanese families with the PCS syndrome. Monoallelic BUBR1 mutations were found in all seven families studied: a single-base deletion (1833delT) in four families; and a splice site mutation, a nonsense mutation, and a missense mutation in one family each. Transcripts derived from the patients with the 1833delT mutation and the splice site mutation were significantly reduced, probably due to nonsense-mediated mRNA decay. No mutation was found in the second alleles in the seven families studied, but RT-PCR of BUBIB and Western blot analysis of BubR1 indicated a modest decrease of their transcripts. BubR1 in the cells from two patients showed both reduced protein expression and diminished kinetochore localization. Their expression level of p55cdc, a specific activator of anaphase-promoting complex, was normal but its kinetochore association was abolished. Microcell-mediated transfer of chromosome 15 (containing BUB1B into the cells restored normal BubR1 levels, kinetochore localization of p55cdc, and the normal responses to colcemid treatment. These findings indicate the involvement of BubR1 in p55cdc-mediated mitotic checkpoint signaling, and suggest that > 50% decrease in expression (or activity) of BubR1 is involved in the PCS syndrome. (c) 2006 Wiley-Liss, Inc., WILEY-LISS
American Journal of Medical Genetics, 2006, [Reviewed]

53BP1 contributes to survival of cells irradiated with X-ray during G1 without Ku70 or Artemis
Iwabuchi; K.; Hashimoto; M.; Matsui; T.; Kurihara; T.; Shimizu; H.; Adachi; N.; Ishiai; M.; Yamamoto; K.; Tauchi; H.; Takata; M.; Koyama; H.; Date; T., Ionizing radiation (IR) induces a variety of DNA lesions. The most significant lesion is a DNA double-strand break (DSB), which is repaired by homologous recombination or nonhomologous end joining (NHEJ) pathway. Since we previously demonstrated that IR-responsive protein 53BP1 specifically enhances activity of DNA ligase IV, a DNA ligase required for NHEJ, we investigated responses of 53BP1-deficient chicken DT40 cells to IR. 53BP1-deficient cells showed increased sensitivity to X-rays during G1 phase. Although intra-S and G2/M checkpoints were intact, the frequency of isochromatid-type chromosomal aberrations was elevated after irradiation in 53BP1-deficient cells. Furthermore, the disappearance of X-ray-induced gamma-H2AX foci, a marker of DNA DSBs, was prolonged in 53BP1-deficient cells. Thus, the elevated X-ray sensitivity in G1 phase cells was attributable to repair defect for IR-induced DNA-damage. Epistasis analysis revealed that 53BP1 plays a role in a pathway distinct from the Ku-dependent and Artemis-dependent NHEJ pathways, but requires DNA ligase IV. Strikingly, disruption of the 53BP1 gene together with inhibition of phosphatidylinositol 3-kinase family by wortmannin completely abolished colony formation by cells irradiated during G1 phase. These results demonstrate that the 53BP1-dependent repair pathway is important for survival of cells irradiated with IR during the G1 phase of the cell cycle., BLACKWELL PUBLISHING
Genes to Cells, 2006, [Reviewed]

Association of Ionizing Radiation-Induced Foci of NBS1 with Chromosomal Instability and Breast Cancer Susceptibility
Someya; M.; Sakata; K.; Tauchi; H.; Matsumoto; Y.; Nakamura; A.; Komatsu; K.; Hareyama; M., NBS1, a protein essential for DNA double-strand break repair, relocalizes into subnuclear structures upon induction of DNA damage by ionizing radiation, forming ionizing radiation-induced foci. We compared radiation-induced NBS1 foci in peripheral blood lymphocytes (PBLs) from 46 sporadic breast cancer patients and 30 healthy cancer-free volunteers. The number of persistent radiation-induced NBS1 foci per nucleus at 24 h after irradiation for patients with invasive cancer was significantly higher than for normal healthy volunteers. The frequency of spontaneous chromosome aberration increased as the number of persistent radiation-induced NBS1 foci increased, indicating that the number of persistent radiation-induced NBS1 foci might be associated with chromosome instability. There was also an inverse correlation between the number of radiation-induced NBS1 foci and the activity of DNA-dependent protein kinase (DNA-PK), which plays an important role in the nonhomologous end-joining (NHEJ) path-way, another mechanism of DNA DSB repair, indicating a close interrelationship between homologous recombination (HR) and NHEJ in DNA DSB repair. In conclusion, the number of persistent radiation-induced NBS1 foci is associated with chromosomal instability and risk of sporadic breast cancer and hence might be used to select individuals for whom a detailed examination is necessary because of their increased susceptibility to breast cancer, although refinement of the techniques for technical simplicity and accuracy will be required for clinical use. (c) 2006 by Radiation Reseacch Society., RADIATION RESEARCH SOC
Radiation Research, 2006, [Reviewed]

ATM activation by a sulfhydryl-reactive inflammatory cyclopentenone prostaglandin
Kobayashi; M.; Ono; H.; Mihara; K.; Tauchi; H.; Komatsu; K.; Shibata; T.; Shimizu; H.; Uchida; K.; Yamamoto; K., ATM (ataxia-telangiectasia mutated) is activated by a variety of noxious agent, including oxidative stress, and ATM deficiency results in an anomalous cellular response to oxidative stress. However, the mechanisms for ATM activation by oxidative stress remain to be established. Furthermore, it is not clear whether ATM responds to oxidative DNA damage or to a change in the intracellular redox state, independent of DNA damage. We found that ATM is activated by N-methyl-N'-nitro-nitrosoguanidine (MNNG) and 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), in NBS1- or MSH6-deficient cells. We further found that ATM is activated by treating chromatin-free immunoprecipitated ATM with MNNG or 15d-PGJ(2), which modifies free sulfhydryl (SH) groups, and that 15d-PGJ(2) binds covalently to ATM. Interestingly, 15d-PGJ(2)-induced ATM activation leads to p53 activation and apoptosis, but not to Chk2 or H2AX phosphorylation. These results indicate that ATM is activated through the direct modification of its SH groups, independent of DNA damage, and this activation leads, downstream, to apoptosis., BLACKWELL PUBLISHING
GENES TO CELLS, 2006, [Reviewed]

Activation of Antioxidative Enzymes Induced by Low-Dose-Rate Whole-Body gamma Irradiation: Adaptive Response in Terms of Initial DNA Damage
Otsuka; K.; Koana; T.; Tauchi; H.; Sakai; K., An adaptive response induced by long-term low-dose-rate irradiation in mice was evaluated in terms of the amount of DNA damage in the spleen analyzed by a comet assay. C57BL/6N female mice were irradiated with 0.5 Gy Of (CS)-C-137 gamma rays at 1.2 mGy/h; thereafter, a challenge dose (0.4, 0.8 or 1.6 Gy) at a high dose rate was given. Less DNA damage was observed in the spleen cells of preirradiated mice than in those of mice that received the challenge dose only; an adaptive response in terms of DNA damage was induced by long-term low-dose-rate irradiation in mice. The gene expression of catalase and Mn-SOD was significantly increased in the spleen after 23 days of the low-dose-rate radiation (0.5 Gy). In addition, the enzymatic activity of catalase corresponded to the gene expression level; the increase in the activity was observed at day 23 (0.5 Gy). These results suggested that an enhancement of the antioxidative capacities played an important role in the reduction of initial DNA damage by low-dose-rate radiation. (c) 2006 by Radiation Research Society., RADIATION RESEARCH SOC
Radiation Research, 2006, [Reviewed]

Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress
Nakano; T.; Katafuchi; A.; Shimizu; R.; Terato; H.; Suzuki; T.; Tauchi; H.; Makino; K.; Skorvaga; M.; Van Houten; B.; Ide; H.:, Nitric oxide (NO) induces deamination of guanine, yielding xanthine and oxanine (Oxa). Furthermore, Oxa reacts with polyamines and DNA binding proteins to form cross-link adducts. Thus, it is of interest how these lesions are processed by DNA repair enzymes in view of the genotoxic mechanism of NO. In the present study, we have examined the repair capacity for Oxa and Oxa-spermine cross-link adducts (Oxa-Sp) of enzymes involved in base excision repair (BER) and nucleotide excision repair (NER) to delineate the repair mechanism of nitrosative damage to guanine. Oligonucleotide substrates containing Oxa and Oxa-Sp were incubated with purified BER and NER enzymes or cell-free extracts (CFEs), and the damage-excising or DNA-incising activity was compared with that for control (physiological) substrates. The Oxa-excising activities of Escherichia coli and human DNA glycosylases and HeLa CFEs were 0.2-9% relative to control substrates, implying poor processing of Oxa by BER. In contrast, DNA containing Oxa-Sp was incised efficiently by UvrABC nuclease and SOS-induced E.coli CFEs, suggesting a role of NER in ameliorating genotoxic effects associated with nitrosative stress. Analyses of the activity of CFEs from NER-proficient and NER-deficient human cells on Oxa-Sp DNA confirmed further the involvement of NER in the repair of nitrosative DNA damage., OXFORD UNIV PRESS
Nucleic Acids Research, 2005, [Reviewed]

Uptake of heavy water and loss bay tangerine in the heavy water vapor release experiment in a greenhouse as a substitute for tritiated water
Ichimasa Y.; Sasajima; E.; Makihara; H.; Tauchi; H.; Uda; T.; Ichimasa; M., Heavy water (D2O) vapor release experiments were carried out in a greenhouse using deuterium as a substitute for tritium and uptake and loss kinetics of D2O in leaf of a tangerine tree and formation, translocation and retention of organically bound deuterium (OBD) in tangerine exposed to D2O under different growth stage were investigated. Rate constants of D2O uptake in leaves of tangerine were 0.2 - 1.11 hr(-1) in the daytime release and 0.03-0.12 hr(-1) in the nighttime release. Rate constants of D2O loss in leaf after daytime release were almost the same as those after the nighttime release. No significant differences in the half time of D2O loss were observed between daytime and nighttime releases, but those in winter experiments were about 6 times higher than those in summer ones. The retention of OBD of the edible part of tangerine at harvest was very low and OBD was 0.08% or 0.07% on average of D2O in air moisture in daytime or nighttime releases., AMER NUCLEAR SOCIETY
Fusion Science and Technology, 2005, [Reviewed]

Recognition of DNA damage by NBS1/hMRE11/hRAD50 complex
Kobayashi Junya; Tauchi Hiroshi; Chen Benjamin; Sakamoto Shuichi; Matsuura Shinya; Chen David; Komatsu Kenshi
CELL STRUCTURE AND FUNCTION, May 2004, [Reviewed]

Analysis of cells from the patients with PCS (premature chromatid separation) syndrome
Matsumoto Yoshiyuki; Morishima Ken-ichi; Kobayashi Junya; Tauchi Hiroshi; Komatsu Kenshi; Ikeuchi Tatsuro; Kajii Tadashi; Matsuura Shinya, PCS syndrome is the human mitotic-spindle checkpoint disorder, characterized by mosaic variegated aneuploidy (MVA) and premature chromatid separation (PCS). The clinical manifestations include severe microcephaly, Dandy-Walker anomaly, and development of Wilms tumor. To determine the molecular basis of the disorder, we established immortalized skin fibroblast cell lines from Japanese patients. We found that the expression level of BubR1 protein was remarkably decreased in PCS cells, and only faint BubR1 signals were detected on kinetochores by immunofluorescence analysis. In PCS cells, p55cdc also failed to associate with the kinetochores. These abnormal features were normalized after introduction of BubR1 cDNA. Sequence analysis of the patients' cells detected no mutations in the BubR1 gene. These results indicated that the reduced expression of BubR1 protein might result in abolished kinetochore localization of p55cdc, and cause the mitotic checkpoint defects in PCS cells., Journal of Radiation Research Editorial Committee
The Japan Radiation Research Society Annual Meeting Abstracts, 2004

NBS1を中心とした放射線DNA二重鎖切断修復遺伝子の機能解析　　　　　　　　　　　　　　　
田内 広; 飯島健太; 坂本修一; 小松賢志
茨城大・理・地球生命環境科学，京大放生研, 2004, [Reviewed]

Nijmegen breakage syndrome and DNA double strand break repair by NBS1 complex
Matsuura; S.; Kobayashi; J.; Tauchi; H.; Komatsu; K, JAPAN SCIENTIFIC SOC PRESS
Advances in Biophysics, 2004

The Nijmegen breakage syndrome gene and its role in genome stability
Iijima; K.; Komatsu; K.; Matsuura; S.; Tauchi; H., Corresponding, NBS1 is the key regulator of the RAD50/ MRE11/NBS1 (R/M/N) protein complex, a sensor and mediator for cellular DNA damage response. NBS1 potentiates the enzymatic activity of MRE11 and directs the R/M/N complex to sites of DNA damage, where it forms nuclear foci by interacting with phosphorylated H2AX. The R/M/N complex also activates the ATM kinase, which is a major kinase involved in the activation of DNA damage signal pathways. The ATM requires the R/M/N complex for its own activation following DNA damage, and for conformational change to develop a high affinity for target proteins. In addition, association of NBS1 with PML, the promyelocytic leukemia protein, is required to form nuclear bodies, which have various functions depending on their location and composition. These nuclear bodies function not only in response to DNA damage, but are also involved in telomere maintenance when they are located on telomeres. In this review, we describe the role of NBS1 in the maintenance of genetic stability through the activation of cell-cycle checkpoints, DNA repair, and protein relocation., SPRINGER
Chromosoma, 2004

NBS1 and its functional role in the DNA damage response
Kobayashi; J.; Antoccia; A.; Tauchi; H.; Matsuura; S.; Komatsu; K., Nijmegen breakage syndrome is a recessive genetic disorder, characterized by elevated sensitivity to ionizing radiation, chromosome instability and high frequency of malignancies. Since cellular features partly overlap with those of ataxia-telangiectasia (A-T), NBS was long considered an A-T clinical variant. NBS1, the product of the gene underlying the disease, contains three functional regions: the forkhead-associated (FHA) domain and BRCA1 C-terminus (BRCT) domain at the N-terminus, several SQ motifs (consensus phosphorylation sites by ATM and ATR kinases) at a central region and MRE11-binding region at the C-terminus. NBS I forms a multimeric complex with hMRE11/hRAD50 nuclease at the C-terminus and recruits or retains them at the vicinity of sites of DNA damage by direct binding to histone H2AX, which is phosphorylated by ATM in response to DNA damage. The combination of the FHA/BRCT domains has a crucial role for the binding of NBS1 to H2AX. Thereafter, the NBS1 complex proceeds to rejoin double-strand breaks predominantly by homologous recombination repair in vertebrates. while it also might be involved in suppression of inter-chromosomal recombination even for V(D)J recombination. These processes collaborate with cell cycle checkpoints to facilitate DNA repair, while defects of these checkpoints in NBS cells are partial in nature. A possible explanation for these moderate defects are the redundancy of multiple checkpoint regulations in vertebrates, or the modulator role of NBS1. in which NBS1 amplifies ATM activation by accumulation of the MRN complex at damaged sites. This molecular link of NBS1 to ATM may explain the phenotypic similarity of NBS to A-T. (C) 2004 Elsevier B.V. All rights reserved., ELSEVIER SCIENCE BV
DNA Repair, 2004

242 Analysis of apoptosis induction in Nbs1 deficient cells(Apoptosis related, Abstracts of the 46th Annual Meeting of the Japan Radiation Research Society)
OGATA Hiromi; MURANAKA Chizuko; SAKAMOTO Shuichi; KOBAYASHI Junya; ICHIMASA Michiko; ICHIMASA Yusuke; MATSUURA Shinya; KOMATSU Kenshi; TAUCHI Hiroshi, The Japan Radiation Research Society
Journal of radiation research, 15 Dec. 2003

206 Functional Domain Analysis of NBS1 Gene in Homologous Recombinational Repair(Physics, chemistry and DNA damage, Abstracts of the 46th Annual Meeting of the Japan Radiation Research Society)
IIJIMA Kenta; SAKAMOTO Shuichi; MATSUURA Shinya; KOMATSU Kenshi; ICHIMASA Yusuke; TAUCHI Hiroshi, The Japan Radiation Research Society
Journal of radiation research, 15 Dec. 2003

98 Localization of Rad51 protein in cells from patients with Fanconi Anemia D1 group(Repair of radiation damage, Abstracts of the 46th Annual Meeting of the Japan Radiation Research Society)
MORISHIMA Kenichi; NAKAMURA Asako; SAKAMOTO Syuichi; TAUCHI Hiroshi; ANTOCCIA Antonio; MATSUURA Shinya; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, 15 Dec. 2003

S-3-1 Mechanisms of DNA double-strand break repair(Biological Effects of Low Dose and Low Dose-rate Irradiations, Abstracts of the 46th Annual Meeting of the Japan Radiation Research Society)
TAUCHI Hiroshi; KOBAYASHI Junya; MURANAKA Chizuko; SAKAMOTO Shuichi; GENT Dik; ICHIMASA Yusuke; MATSUURA Shinya; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, 15 Dec. 2003

Effect of gravity stress on fidelity of DNA double-strand break repair.
H. Tauchi; E. Matsumoto; K. Iijima; D. Mochizuki; K. Komatsu; Y. Ichimasa, DNA double strand break (DSB) causes many cytotoxic effects such as cellular lethality, somatic mutation, and carcinogenesis. Fidelity of DSB repair is a important factor that determines the quality of genomic stability. It is known that the most of DSBs are properly repaired on the earth, however, little is known whether those are rejoined at the same fidelity even under the space environment. One of the DSB repair pathway, homologous recombination (HR), allows the cells to repair their DSBs with error free. Therefore, the efficiency of HR is a good index to assess the fidelity of DSB repair. In order to clarify the effect of gravity stress on HR pathway, we established a cell line that can detect a site-specific DNA repair via HR. The cells carrying a reporter construct for HR were incubated under hypergravity condition after induction of site specific DSB. Our preliminary results suggest that the gravity stress may affect the HR efficiency.
Biological sciences in space, 2003, [Reviewed]

p16 gene transfer increases cell killing with abnormal nucleation after ionizing radiation in glioma cells
Hama; S.; Matsuura; S.; Tauchi; H.; Yamasaki; F.; Kajiwara; Y.; Arita; K.; Yoshioka; H.; Heike; Y.; Mandai; K.; Kurisu; K, It is well established that cells synchronised at the G1 - S phase are highly radiosensitive. In this study, p16-null human glioma cell lines were induced into G1 cell cycle arrest by adenovirus-mediated p16 gene transfer, and examined for radiation-induced cell killing. Clonogenic analysis and trypan blue extraction test showed that the p16 gene transfer enhanced radiation-induced cell killing in p16-null glioma cell lines. TUNEL assays and pulse-field gel electrophoresis confirmed that the radiation-induced cell killing of p16-transfected cells could be caused by a nonapoptotic mechanism. Gimsa staining demonstrated that irradiation alone or Ax-mock infection plus irradiation results in a slight increase in the frequency of cells with abnormal nucleus, compared to unirradiated uninfected or Ax-mock infected cells. However, Ax-hp16 or Ax-hp21 infection alone modestly increased the frequency of cells with abnormal nucleus ( especially bi- and multinucleation), and 4-Gy irradiation of Ax-hp16 or Ax-hp21 infected cells substantially enhanced this frequency. These results suggest that there exists some unknown interaction between radiation and p16 in cytoplasm/ membranes, which decreases cytokinesis and promotes abnormal nucleation. Thus, p16 expression prevented radiation-induced apoptosis by promoting abnormal nucleation, thereby leading to another mode of cell death., NATURE PUBLISHING GROUP
British Journal of Cancer, 2003

DNA二重鎖切断の相同組換えによる修復 － 関連するタンパクをめぐる最近の話題 －
飯島健太; 松本英悟; 望月大輔; 田内 広, 放射線生物研究会
放射線生物研究, 2003

Mutation screening for a novel cancer-predisposition syndrome of total PCS
MATSUURA Shinya; TAUCHI Hiroshi; KOBAYASHI Junya; Antoccia Antonio; SHINOHARA Miki; KOMATSU Kenshi; IKEUCHI Tatsuro; KAJII Tadashi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2002

Analysis of the function of NBS1 in DNA double-strand break repair
TAUCHI Hiroshi; KOBAYASHI Junya; Gent an Dik; MATSUURA Shinya; ICHIMASA Michiko; ICHIMASA Yusuke; TAKEDA Shunichi; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2002

Histone H2AX regulates the formation of NBS1 foci on DNA damage sites
KOBAYASHI Junya; TAUCHI Hiroshi; MATSUURA Shinya; NAKAMURA Asako; MORISHIMA Ken-ichi; SAKAMOTO Shuchi; TANIMOTO Keiji; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2002

Dissociation of ATM/NBS1 functions in telomere maintenance
NAKAMURA Asako; TAUCHI Hiroshi; KOBAYASHI Junya; MATSUURA Shinya; IDE Toshinori; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2002

NBS1 is involved in recognition of DNA damage and initiation of homologous recombination.
KOMATSU Kenshi; KOBAYASHI Jyunya; TAUCHI Hiroshi; SAKAMOTO Shuichi; NAKAMURA Asako; MORISIMA Kenichi; MATSUURA Shinya, The Japan Radiation Research Society
Journal of radiation research, Dec. 2002

p53結合蛋白質1(53BP1)はDNA二重鎖切断の修復に関与する　　　　　　　　　　　　　　　
岩淵 邦芳; 栗原 孝行; 柴田 昌夫; 曹 永恒; 濱田 富美男; 小林 純也; 田内 広; 青木 秀年; 本山 昇; 小松 賢志; 今村 幸治; 伊達 孝保, (一社)日本放射線影響学会
日本放射線影響学会大会講演要旨集, Sep. 2002

Studies of mutagenesis caused by low dose rate tritium radiation using a novel hyper-sensitive detection system
Tauchi; H.; Ichimasa; M.; Ichimasa; Y.; Shiraishi; T.; Morishima; K.; Matsuura; S.; Komatsu; K, Lead, A novel hyper-sensitive detection system was developed to detect Hprt-deficient mutations using Hprt deficient hamster fibroblast cells which carry a normal human X-chromosome. The system has been found to be 100-fold more sensitive for detecting mutations than the conventional system which uses an internal Hprt gene. The mutation frequency induced by 1 Gy of tritium radiation at different dose rates (0.9, 0.4, 0.04, and 0.018 Gy/h) was measured. No significant differences in mutation frequencies were observed within the range of dose rates used, suggesting that if a reverse dose-rate effect exists, it may not be observable with tritium radiation at dose rates over 0.018 Gy/h. Interestingly, molecular analysis of the Hprt locus in Hprt-deficient mutants induced by tritium showed that deletion sizes observed in the hamster cell's human X-chromosome under these conditions are much smaller in cells exposed at 0.04 (and 0.018 Gy/h) than in cells exposed at 0.9 Gy/h. This phenomenon seems to be specific for tritium radiation because it was not apparent after exposure to gamma-rays. The novel hyper-sensitive detection system used here is useful for analysis of the mutagenic effects of low doses of tritium radiation delivered at low dose rates., AMER NUCLEAR SOCIETY
Fusion Science and Technology, 2002

Nbsl is essential for DNA repair by homelogous recombination in hygher vertebrate cells
H Tauchi; J Kobayashi; K Morishima; DC van Gent; T Shiraishi; NS Verkaik; D vanHeems; E Ito; A Nakamura; E Sonodo; M Takata; S Takeda; S Matsuura; K Komatsu, Lead, Double-strand breaks occur during DNA replication and are also induced by ionizing radiation. There are at least two pathways which can repair such breaks: non-homologous end joining and homologous recombination (HR). Although these pathways are essentially independent of one another, it is possible that the proteins Mre11, Rad50 and Xrs2 are involved in both pathways in Saccharomyces cerevisiae(1). In vertebrate cells, little is known about the exact function of the Mre11-Rad50-Nbs1 complex in the repair of double-strand breaks because Mre11-andRad50-null mutations are lethal(2). Here we show that Nbs1 is essential for HR-mediated repair in higher vertebrate cells. The disruption of Nbs1 reduces gene conversion and sister chromatid exchanges, similar to other HR-deficient mutants(3). In fact, a site-specific double-strand break repair assay showed a notable reduction of HR events following generation of such breaks in Nbs1-disrupted cells. The rare recombinants observed in the Nbs1-disrupted cells were frequently found to have aberrant structures, which possibly arise from unusual crossover events, suggesting that the Nbs1 complex might be required to process recombination intermediates., NATURE PUBLISHING GROUP
Nature, 2002

NBSl localizes to γ-H2AX foci through interaction with FHA/BRCT domain
J Kobayashi; H Tauchi; S Sakamoto; A Nakamura; K Morishima; S Matsuura; T Kobayashi; K Tamai; K Tanimoto; K Komatsu, DNA double-strand breaks represent the most potentially serious damage to a genome; hence, many repair proteins are recruited to nuclear damage sites by as yet poorly characterized sensor mechanisms. Here, we show that NBS1, the gene product defective in Nijmegen breakage syndrome (NBS) [1-3], physically interacts with histone, rather than damaged DNA, by direct binding to gamma-H2AX. We also demonstrate that NBS1 binding can occur in the absence of interaction with hMRE11 or BRCA1. Furthermore, this NBS1 physical interaction was reduced when anti-gamma-H2AX antibody was introduced into normal cells and was also delayed in AT cells, which lack the kinase activity for phosphorylation of H2AX. NBS1 has no DNA binding region but carries a combination of the fork-head associated (FHA) and the BRCA1 C-terminal domains (BRCT) [4]. We show that the FHA/BRCT domain of NBS1 is essential for this physical interaction, since NBS1 lacking this domain failed to bind to gamma-H2AX in cells, and a recombinant FHA/BRCT domain alone can bind to recombinant 7-H2AX. Consequently, the FHA/BRCT domain is likely to have a crucial role for both binding to histone and for relocalization of hMRE11/hRAD50 nuclease complex to the vicinity of DNA damage., CELL PRESS
Current Biology, 2002

Nijmegen breakage syndrome gene, NBS1, and molecular links to factors for genome stability
Tauchi; H.; Matsuura; S.; Kobayashi; J.; Sakamoto; S.; Komatsu; K., Lead, DNA double-strand breaks represent the most potentially serious damage to a genome and hence, at least two pathways of DNA repair have evolved; namely, homologous recombination repair and non-homologous end joining. Defects in both rejoining processes result in genomic instability including chromosome rearrangements, LOH and gene mutations, which may lead to development of malignancies. Nijmegen breakage syndrome is a recessive genetic disorder, characterized by elevated sensitivity to ionizing radiation that induces double-strand breaks, and high frequency of malignancies. NBS1, the product of the gene underlying the disease, forms a multimeric complex with hMRE11/ hRAD50 nuclease and recruits them to the vicinity of sites of DNA damage by direct binding to phosphorylated histone H2AX. The combination of the highly-conserved NBS1 forkhead associated domain and BRCA1 C-terminus domain has a crucial role for recognition of damaged sites. Thereafter, the NBS1-complex proceeds to rejoin double-strand breaks predominantly by homologous recombination repair in vertebrates. This process collaborates with cell-cycle checkpoints at S and G2 phase to facilitate DNA repair. NBS1 is also associated with telomere maintenance and DNA replication. Based on recent knowledge regarding NBS1, we propose here a two-step binding mechanism for damage recognition by repair proteins, and describe the molecular links to factors for genome stability., NATURE PUBLISHING GROUP
Oncogene, 2002

Bystander mutagenic effect of alpha particle in human-hamster hybrid cells
SHIRAISHI Takahiro; TAUCHI Hiroshi; SHINOHARA Miki; MATSUURA Shinya; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2001

Somatic Mutation Caused by Low Dose Rate Tritium Radiation : Studies Using A Hyper-sensitive DetectionSystem
TAUCHI Hiroshi; SHIRAISHI Takahiro; MORISHIMA Kenichi; MATSUURA Shinya; ICHIMASA Michiko; ICHIMASA Yusuke; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2001

Complementation studies of immortalized cell lines from infants with total PCS
ITO Emi; MATSUURA Shinya; SHINOHARA Miki; KOMATSU Kenshi; TAUCHI Hiroshi; IKEUCHI Tatsuro; KAJII Tadashi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2001

Establishement of mouse Nbs1-deficient cell lines by gene targeting
MATSUURA Shinya; ITO Emi; ICHIKAWA Koji; NAKAMURA Asako; KOBAYASHI Junya; TAUCHI Hiroshi; KIMURA Akiro; WATANABE Hiromitsu; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2001

Association of DNA repair protein NBS1 with telomere maintenance
NAKAMURA Asako; TAUCHI Hiroshi; KOBAYASHI Junya; SHINOHARA Miki; MATSUURA Shinya; IDE Toshinori; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2001

The function of NBS1 and histone H2AX in the early process of DNA repair.
KOBAYASHI Junya; TAUCHI Hiroshi; SHINOHARA Miki; MATSUURA Shinya; TANIMOTO Keiji; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2001

Reversed dose-rate effect of high LET radiation in mutation induction
TAUCHI Hiroshi; SHIRAISHI Takahiro; EGUCHI-KASAI Kiyomi; FURUSAWA Yoshiya; ANDO Koichi; MATSUURA Shinya; KOMATSU Kenshi; ICHIMASA Yusuke, The Japan Radiation Research Society
Journal of radiation research, Dec. 2001

The Forkhead-associated domain of NBS1 is essential for nuclear foci formation after irradiation, but not essential for hRAD50/hMRE11/NBS1 complex DNA Repair activity
H Tauchi; J Kobayashi; K Morishima; S Matsuura; A Nakamura; T Shiraishi; E Ito; D Masnada; D Delia; K Komatsu, Lead, NBS1 (p95), the protein responsible for Nijmegen breakage syndrome, shows a weak homology to the yeast Xrs2 protein at the N terminus region, known as the forkhead-associated (FHA) domain and the BRCA1 C terminus domain. The protein interacts with hMRE11 to form a complex with a nuclease activity for initiation of both nonhomologous end joining and homologous recombination. Here, we show in vivo direct evidence that NBS1 recruits the hMRE11 nuclease complex into the cell nucleus and leads to the formation of foci by utilizing different functions from several domains. The amino acid sequence at 665-693 on the C terminus of NBS1, where a novel identical sequence with yeast Xrs2 protein was found, is essential for hMRE11 binding. The hMRE11-binding region is necessary for both nuclear localization of the complex and for cellular radiation resistance. On the other hand, the FHA domain regulates nuclear foci formation of the multiprotein complex in response to DNA damage but is not essential for nuclear transportation of the complex and radiation resistance. Because the FHA/BRCA1 C terminus domain is widely conserved in eukaryotic nuclear proteins related to the cell cycle, gene regulation, and DNA repair, the foci formation could be associated with many phenotypes of Nijmegen breakage syndrome other than radiation sensitivity., AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Journal of Biological Chemistry, 2001

Comparative genomic hybridization analysis suggests a gain of chromosome 7p associated with lymph node metastasis in non-small cell lung cancer
T Ubagai; S Matsuura; H Tauchi; K Itou; K Komatsu, We analyzed the chromosomal gains and losses that occur in 30 non-small cell lung carcinomas by comparative genomic hybridization. Their chromosomal imbalances showed histological type-specific patterns in adenocarcinomas and in squamous cell carcinomas. The genetic changes in non-small cell lung carcinoma were also strongly dependent on metastasis to lymph node. The average numbers of chromosomal alterations were increased from 6.2 to 9.1 along with the presence of metastasis, and it gave rise to the increased copy number in specific chromosomes. In particular, a novel imbalance at 7p12-21 was recognized in a half of carcinoma with metastasis, although no genetic alteration was observed in 15 non-metastasizing lung carcinoma tested here., PROFESSOR D A SPANDIDOS
Oncology Report, 2001

Expression of genes involved in repair of DNA double-strand breaks in normal and tumor tissues
KI Sakata; Y Matsumoto; H Tauchi; M Satoh; A Oouchi; H Nagakura; K Koito; Y Hosoi; N Suzuki; K Komatsu; M Hareyama, Background: DNA double-strand breaks (DSB) are the major lethal lesions induced by ionizing radiation. The capability for DNA DSB repair is crucial for inherent radiosensitivity of tumor and normal cells. DNA-PKcs, Ku 70, Ku 85, Xrcc4, and Nbsl play a critical role in DNA DSB repair.
Methods: We immunohistochemically investigated the expression of DNA-PKcs, Ku 70, Ku85, Xrcc4, and Nbsl in 134 specimens from various normal and tumor tissues with different radiosensitivity.
Results and Conclusion: Immunopositivity to Ku70, Ku85, DNA-PKcs, Xrcc4, and Nbsl was found in all tumor tissues examined. The staining for Ku70, Ku85, and DNA-PKcs was nuclear; but, for Xrcc4 and Nbsl, it was nuclear and cytoplasmic. There were no apparent differences in the expression of these five proteins among cancerous tissues and the corresponding normal tissues. No apparent differences in nuclear staining intensity were detected in the expression of these five proteins among tumor tissues with different radiosensitivity, although non-Hodgkins' lymphoma (B or T cell) tended to show a lower expression than the others. The stromal cells generally expressed these five proteins at much lower frequency than either tumor or epithelial cells in both tumor and normal tissues. (C) 2001 Elsevier Science Inc., ELSEVIER SCIENCE INC
International Journal of Radiation Oncology and Bidogical Physics, 2001

Chk2 activation dependence on Nbsl after DNA damage
G Buscemi; C Savio; L Zannini; F Micciche; D Masnada; M Nakanishi; H Tauchi; K Komatsu; S Mizutani; K Khanna; P Chen; P Concannon; L Chessa; D Delia, The checkpoint kinase Chk2 has a key role in delaying cell cycle progression in response to DNA damage. Upon activation by low-dose ionizing radiation (IR), which occurs in an ataxia telangiectasia mutated (ATM)dependent manner, Chk2 can phosphorylate the mitosis-inducing phosphatase Cdc25C on an inhibitory site, blocking entry into mitosis, and p53 on a regulatory site, causing G, arrest. Here we show that the ATM-dependent activation of Chk2 by gamma- radiation requires Nbs1, the gene product involved in the Nijmegen breakage syndrome (NBS), a disorder that shares with AT a variety of phenotypic defects including chromosome fragility, radiosensitivity, and radioresistant DNA synthesis. Thus, whereas in normal cells Chk2 undergoes a time-dependent increased phosphorylation and induction of catalytic activity against Cdc25C, in NBS cells null for Nbs1 protein, Chk2 phosphorylation and activation are both defective. Importantly, these defects in NBS cells can be complemented by reintroduction of wild-type Nbs1, but neither by a carboxy-terminal deletion mutant of Nbs1 at amino acid 590, unable to form a complex with and to transport Mre11 and Rad50 in the nucleus, nor by an Nbs1 mutated at Ser343 (S343A), the ATM phosphorylation site. Chk2 nuclear expression is unaffected in NBS cells, hence excluding a mislocalization as the cause of failed Chk2 activation in Nbs1-null cells, interestingly, the impaired Chk2 function in NBS cells correlates with the inability, unlike normal cells, to stop entry into mitosis immediately after irradiation, a checkpoint abnormality that can be corrected by introduction of the wild-type but not the S343A mutant form of Nbs1, Altogether, these findings underscore the crucial role of a functional Nbs1 complex in Chk2 activation and suggest that checkpoint defects in NBS cells may result from the inability to activate Chk2., AMER SOC MICROBIOLOGY
Molecular and Cellular Biology, 2001

Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic spindle checkpoint
MATSUURA Shinya; ITO Emi; TAUCHI Hiroshi; IKEUCHI Tatsuro; KAJII Tadashi; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2000

Screening of protein interacting with FANCG by Yeast two-hybrid system
MORISHIMA Ken-ichi; MATSUURA Shinya; NAKAMURA Asako; SHIRAISHI Takahiro; ITO Emi; KOBAYASHI Junya; TAUCHI Hiroshi; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2000

NBS1, the Nijmegen breakage syndrome protein, regulates the localization of DNA repair complex hRAD50/hMRE11/NBS1
SHIRAISHI Takahiro; TAUCHI Hiroshi; KOBAYASHI Junya; MORISHIMA Ken-ichi; NAKAMURA Asako; MATSUURA Shinya; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2000

Accelerated telomere shortening by disruption of DNA repair protein NBS1
NAKAMURA Asako; TAUCHI Hiroshi; MATSUURA Shinya; KOBAYASHI Jyunya; MORISHIMA Kenichi; SHIRAISHI Takahiro; ITO Emi; IDE Toshinori; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2000

Construction of Nbs1 knockout cell line using chicken DT40
TAUCHI Hiroshi; MORISHIMA Ken-ichi; KOBAYASHI Junya; YAMASHITA Yukiko; SONODA Eiichiro; TAKATA Minoru; TAKEDA Shunichi; MATSUURA Shinya; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2000

Function of NBS1 in Activation of ATM kinase in Response to IR.
KOBAYASHI Junya; TAUCHI Hiroshi; MATSUURA Shinya; OGAWA Akira; KOBAYASHI Toshiko; TANIMOTO Keiji; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 2000

Activation of ATM kinase in NBS lymphoblastoid cells
Kobayashi Junya; Tauchi Hiroshi; Matsuura Shinya, Nagasaki University
Nagasaki Igakkai zasshi = Nagasaki medical journal, Sep. 2000

放射線高感受性遺伝病の原因遺伝子NBS1近傍の新規多型マーカーの単離と解析　　　　　　　　　　　　　　　
森島賢一; 松浦伸也; 田内広; 中村麻子; 小松賢志
広島医学, 01 Apr. 2000

機能的相補性試験によるDNA二重鎖切断修復遺伝子NBS1の重要ドメイン解析　　　　　　　　　　　　　　　
田内 広; 伊東淳; 小林; 純也; 森島; 賢一; 中村麻子; 松浦; 伸也; 小松 賢志
広島医学, 01 Apr. 2000

放射線高感受遺伝病NBS近傍の新規多型マーカーの単離と多型解析　　　　　　　　　　　　　　　
森島賢一; 田内広; 松浦伸也; 中村麻子; 小松賢志
広島医学, 01 Apr. 2000, [Reviewed]

ナイミーヘン染色体不安定症候群遺伝子のマウスホモログの単離　　　　　　　　　　　　　　　
松浦伸也; 田内広; 中村麻子; 森島賢一; 小松賢志
広島医学, 01 Apr. 2000

ナイミーヘン染色体不安定症候群(NBS)におけるテロメア維持機構　　　　　　　　　　　　　　　
中村麻子; 田内広; 小林純也; 松浦伸也; 井出利憲; 小松賢志
広島医学, 01 Apr. 2000

NBS細胞およびAT細胞におけるガンマ線誘導アポトーシス　　　　　　　　　　　　　　　
小林純也; 藤田和志; 田内広; 松浦伸也; 小松賢志; 谷本啓二
広島医学, 01 Apr. 2000

Positional cloning and functional analysis of the gene responsible for nijmegen breakage syndrome, NBS1
H Tauchi, Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, combined immunodeficiency, and a high incidence of lymphoid tumor. Cells from NBS patients show chromosomal instability, hypersensitivity to ionizing radiation and abnormal p53-mediated cell cycle regulation. We cloned the underlying gene for NBS, designated NBS1, by complementation-assisted positional cloning from the candidate region 8q21. Large genomic sequencing, as well as a search using computer programs, provides a powerful approach for identifying the underlying gene for a disease. The NBS1 gene encodes a protein of 754 amino acids that has FHA acid BRCT domains which often are conserved in cell-cycle checkpoint proteins. The gene has weak homology to the yeast (Saccharomyces cerevisiae) Xrs2 protein in the N-terminus region. Like yeast Xrs2, the NBS1 protein forms a complex with hRAD50/ hMRE11, and the complex is condensed as foci in the nucleus after irradiation, indicative that this triple-complex is a crucial factor in DNA repair. Functional analysis of the NBS1 protein is in progress and it should provide further clues to understanding the repair mechanism of radiation-induced DNA double-strand breaks., JAPAN RADIATION RESEARCH SOC
JOURNAL OF RADIATION RESEARCH, Mar. 2000

Enhanced mutation of HPRT locus by ionizing radiation in combination with high gravity　　　　　　　　　　　　　　　
K. Komatsu; H. Tauchi; M. Ueda; S. Matsuura
Uchu seibutsu kagaku, 2000, [Reviewed]

Positional cloning and functional analysis of the gene for Nijmegen breakage syndrome,NBS1.
Tauchi; H., Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, combined immunodeficiency, and a high incidence of lymphoid tumor. Cells from NBS patients show chromosomal instability, hypersensitivity to ionizing radiation and abnormal p53-mediated cell cycle regulation. We cloned the underlying gene for NBS, designated NBS1, by complementation-assisted positional cloning from the candidate region 8q21. Large genomic sequencing, as well as a search using computer programs, provides a powerful approach for identifying the underlying gene for a disease. The NBS1 gene encodes a protein of 754 amino acids that has FHA and BRCT domains which often are conserved in cell-cycle checkpoint proteins. The gene has weak homology to the yeast (Saccharomyces cerevisiae) Xrs2 protein in the N-terminus region. Like yeast Xrs2, the NBS1 protein forms a complex with hRAD50/ hMRE11, and the complex is condensed as foci in the nucleus after irradiation, indicative that this triple-complex is a crucial factor in DNA repair. Functional analysis of the NBS1 protein is in progress and it should provide further clues to understanding the repair mechanism of radiation-induced DNA double-strand breaks., Japan Radiation Research Society
Journal of Radiation Ressearch, 2000

Altered splicing of the ATDC message in AT group D cells results in the absence of a functional protein.
Tauchi; H.; Green; C.; Knapp; M.; Laderoute; K.; Kapp; L., The ATDC gene was cloned using functional complementation and complements the radiosensitivity of ataxia telangiectasia (AT) group D cells, Although a number of transcripts have been detected, only a 3.0 kb cDNA found in a HeLa cell cDNA library has been cloned. Since AT group D cells express only a 2.4 kb transcript, efforts were made to clone and sequence this transcript. Using a biotinylated oligonucleotide probe, mRNA preparations were enriched in ATDC-related sequences. After this enrichment, 2.4 kb clones were obtained from the resulting library, The 2.4 kb transcript appears to be untranslated, since no protein from this transcript has been detected in AT group D cells, and this transcript is probably nonfunctional, since a splicing variation has positioned part of intron 1 near the first methionine codon in exon 1, eliminating most of exon 1 and important functional regions from this transcript. This transcript now has a stop codon located 33 bp in front of the first methionine, which would stop translation after the eleventh amino acid. As a result of these changes, the AT group D cell line (AT5BI) expresses no functional ATDC protein., OXFORD UNIV PRESS
Mutagenesis, 2000

Mutation spectrum of MSH3-deficient HHUA/chr.2 cells refrects in vivo activity of the MSH3 gene product in mismatch repair.
Tauchi; H.; Komatsu; K.; Ishizaki; K.; Yatagai; F.; Kato; T., Lead, The endometrial tumor cell line HHUA carries mutations in two mismatch repair (MMR) genes MSH3 and MSH6. We have established an MSH3-deficient HHUA/chr.2 cell line by introducing human chromosome 2, which carries wild-type MSH6 and MSH2 genes, to HHUA cells. Introduction of chromosome 2 to HHUA cells partially restored G:G MMR activity to the cell extract and reduced the frequency of mutation at the hypoxanthine-guanine phosphoribosyltransferase (hprt*) locus to about 3% that of the parental HHUA cells, which is five-fold the frequency in MMR-proficient cells, indicating that the residual mutator activity in HHUA/chr.2 is due to an MSH3-deficiency in these cells. The spectrum of mutations occurring at the HPRT locus of HHUA/chr.2 was determined with 71 spontaneous 6TG(r) clones. Base substitutions and +/-1 bp frameshifts were the major mutational events constituting, respectively, 54% and 42% of the total mutations, and more than 70% of them occurred at A:T sites. A possible explanation for the apparent bias of mutations to A:T sites in HHUA/chr.2 is haploinsufficiency of the MSH6 gene on the transferred chromosome 2. Comparison of the mutation spectra of HHUA/chr.2 with that of the MSH6-deficient HCT-15 cell Line [S. Ohzeki, A. Tachibana, K. Tatsumi, T. Kato, Carcinogenesis 18 (1997) 1127-1133.] suggests that in vivo the MutS alpha (MSH2:MSH6) efficiently repairs both mismatch and unpaired extrahelical bases, whereas MutS beta (MSH2:MSH3) efficiently repairs extrahelical bases and repairs mismatch bases to a limited extent. (C) 2000 Elsevier Science B.V. All rights reserved., ELSEVIER SCIENCE BV
Mutation Research, 2000

Heat-induced accumulation of p53 and hsp72 is suppressed in lung fibroblasts from SCID mouse
T Ohnishi; K Komatsu; H Tauchi; Wang, X; A Takahashi; K Ohnishi; A Shiba; H Matsumoto, Purpose: To investigate how DNA-dependent protein kinase (DNA-PK) contributes to p53-dependent signal transduction after heat shock, thermosensitivity and accumulation of p53 and hsp72 after heat shock in lung fibroblasts derived from the SCID mouse were analysed.
Materials and methods: Thermosensitivity at 44 degrees C in colony-forming units and Western blot analysis of p53 and hsp72 were analysed.
Results: The results indicated that (1) the thermosensitivity at 44 degrees C of SCID cells was higher than that of parental cells and (2) heat-induced accumulation of p53 and hsp72 was abolished and suppressed in SCID cells as compared with that in parental cells respectively.
Conclusions: The findings suggest that the catalytic subunit of DNA-PK may play an important role upstream of p53 and hsp72, which are possible determinants of cellular thermosensitivity., TAYLOR & FRANCIS LTD
International Journal of Radiation Biology, 2000

Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic-spindle checkpoint
S Matsuura; E Ito; H Tauchi; K Komatsu; T Ikeuchi; T Kajii, Skin fibroblast cells from two unrelated male infants with a chromosome-instability disorder were analyzed for their response to colcemid-induced mitotic-spindle checkpoint. The infants both had severe growth and developmental retardation, microcephaly, and Dandy-Walker anomaly; developed Wilms tumor; and one died at age 5 mo, the other at age 3 years. Their metaphases had total premature chromatid separation (total PCS) and mosaic variegated aneuploidy. Mitotic-index analysis of their cells showed the absence of mitotic block after the treatment with colcemid, a mitotic-spindle inhibitor. Bromodeoxyuridine-incorporation measurement and microscopic analysis indicated that cells treated with colcemid entered G1 and S phases without sister-chromatid segregation and cytokinesis. Preparations of short-term colcemid-treated cells contained those cells with chromosomes in total PCS and all or clusters of them encapsulated by nuclear membranes. Cell-cycle studies demonstrated the accumulation of cells with a DNA content of 8C. These findings indicate that the infants' cells were insensitive to the colcemid-induced mitotic-spindle checkpoint., UNIV CHICAGO PRESS
American Journal of Human Genetics, 2000

Absence of mutation in the NBS1 gene in B-cell malignant lymphoma patients
S Hama; S Matsuura; H Tauchi; J Sawada; C Kato; F Yamasaki; H Yoshioka; K Sugiyama; K Arita; K Kurisu; N Kamada; Y Heike; K Komatsu, Background: Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation severe combined immunodeficiency and a high incidence of lymphoid carcinoma, the majority of which are B-cell lymphomas. To determine whether the NBS1 gene is a tumor suppressor gene in B-cell lymphoma we screened B-cell malignant lymphoma (ML) for any evidence of NBS1 mutation. Materials and methods: Sequence analysis of the NBS1 gene was performed from PCR products amplified from the DNA of 12 extracranial ML or RT=PCR products amplified from cDNA of 8 primary central nervous system lymphoma. Results: Direct sequence analysis revealed that no NBS1 mutations were present in any of these patients. Conclusion: The present results suggested that the contribution of NBS1 mutations to B-cell ML was minimal, despite the fact that the NBS1 gene was causative factor in these cases., INT INST ANTICANCER RESEARCH
Anticancer Research, 2000

NBS1 Regulates Apoptosis induced by ɤ-irradiation in Lymphoblastoid
FUKAMI-KOBAYASHI Junya; FUJITA Kazushi; TAUCHI Hiroshi; MATSUURA Shinya; KOMATSU Kenshi; TANIMOTO Keiji, The Japan Radiation Research Society
Journal of radiation research, Dec. 1999

Mutation screening of the NBS1 gene in sporadic malignant lymphoma
MATSUURA Shinya; KATO Chikage; SAWADA Junko; TAUCHI Hiroshi; NAKAMURA Asako; MORISHIMA Ken-ichi; KAMADA Nanao; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1999

Functionally important domain analysis of the Nijimegen breakage syndrome gene. NBS1
TAUCHI Hiroshi; ITOH Atsushi; KOBAYASHI Junya; MORISHIMA Ken-ichi; NAKAMURA Asako; MATSUURA Shinya; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1999

Mapping of the underlying gene for rare genetic complementation group Fanconi anemia
MORISHIMA Ken-ichi; MATSUURA Shinya; TAUCHI Hiroshi; NAKAMURA Asako; TSUYAMA Naohiro; OSHIMURA Mitsuo; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1999

Development of a Radio-sensitive Mutation System for the Study of Dose Rate Effects of Space High LET Radiation
KOMATSU Kenshi; TAUCHI Hiroshi; NAKAMURA Asako; MORISHIMA Kenichi; UEDA Miki; KOBAYASHI Junya; KASAI Kiyomi E; ANDO Koichi; MATSUURA Shinya, The Japan Radiation Research Society
Journal of radiation research, Dec. 1999

LET, cell cycle dependence for mutation induction and spectrum in HPRT locus
TAUCHI Hiroshi; EGUCHI-KASAI Kiyomi; FRUSAWA Yoshiya; SUZUKI Masao; ANDO Koichi; ENDO Satoru; SAWADA Shozo; MATSUURA Shinya; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1999

High LET radiation-indcued cellular transformation and analysis of inversed dose rate effects by using(hamster x human X-chromosome) hybrid cells.
KOMATSU Kenshi; TAUCHI Hiroshi; UEDA Miki; NAKAMURA Asako; MORISHIMA Kenichi; KOBAYASHI Junnya; KASAI Kiyomi E; ANDO Koichi; MATSURA Shinya
Biological sciences in space, Sep. 1999

Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer
T. Hiramoto; T. Nakanishi; T. Sumiyoshi; T. Fukuda; S. Matsuura; H. Tauchi; K. Komatsu; Y. Shibasaki; H. Inui; M. Watatani; M. Yasutomi; K. Sumii; G. Kajiyama; N. Kamada; K. Miyagawa; K. Kamiya
Oncogene, 1999, [Reviewed]

A polymorphic CA repeat marker at the human 27-kD calbindin (CALB1) locus
K.-I. Morishima; S. Matsuura; H. Tauchi; A. Nakamura; K. Komatsu
Journal of Human Genetics, 1999, [Reviewed]

Neutron generator (HIRRAC) and dosimetry study.
Endo, S; Hoshi, M; Takada, J; Tauchi, H; Matsuura, S; Takeoka, S; Kitagawa, K; Suga, S; Komatsu, K, Dosimetry studies have been made for neutrons from a neutron generator at Hiroshima University (HIRRAC) which is designed for radiobiological research. Neutrons in an energy range from 0.07 to 2.7 MeV are available for biological irradiations. The produced neutron energies were measured and evaluated by a 3He-gas proportional counter. Energy spread was made certain to be small enough for radiobiological studies. Dose evaluations were performed by two different methods, namely use of tissue equivalent paired ionization chambers and activation of method with indium foils. Moreover, energy deposition spectra in small targets of tissue equivalent materials, so-called lineal energy spectrum, were also measured and are discussed. Specifications for biological irradiation are presented in terms of monoenergetic beam conditions, dose rates and deposited energy spectra.
Journal of radiation research, 01 Jan. 1999

Sequence analysis of an 800-kb genomic DNA region on chromosome 8q21 that contains the Nijmegen breakage syndrome gene, NBS1
Tauchi; H.; Mastuura; S.; Isomura; M.; Kinjo; T.; Nakamura; A.; Sakamoto; S.; Kondo; N.; Endo; S.; Komatsu; K.; Nakamura Y, Lead, An 800-kb region on chromosome 8q21, which complements the phenotype of cells from Nijmegen breakage syndrome patients, is a candidate for the locus of the underlying gene, termed NBS1. The sequence of this 800-kb region of DNA indicated that the size of this segment is 755,832 bp with an additional 36-kb gap. From this region, we identified four genes including NBS1, a gene coding for a 27-kDa vitamin D-dependent calcium-binding protein (27-kDa calbindin), the mitochondrial 2,4-dienoyl-CoA reductase gene, and a novel gene, C8orf1/hT41. All four genes were aligned in a 250-kb centromeric portion of the region, and no gene was found in the remaining telomeric portion containing 500 kb. The genomic organization of the C8orf1/hT41 and NBS1 genes has been analyzed using the computer programs GRAIL 2 and GENSCAN. They predicted and successfully found more than 93% of the exons, even a small 54-bp exon, indicating that one or more exons in any gene can be identified by these programs. GENSCAN was more efficient at locating the four genes than GRAIL 2 and identified 15 of the 16 exons of the NBS1 gene. This 800-kb region contained repetitive sequences, including 179 copies of the Alu sequence (1 copy/4.2 kb), 123 copies of the L1 sequence (1 copy/6.1 kb), 107 copies of the LTR sequence (1 copy/7.1 kb), and 63 copies of the MER sequence (1 copy/12 kb). There was a slight but not significant difference in the repetitive content of the gene-rich region and the remaining noncoding region. Our results indicate that computer-assisted methods are useful and powerful for identifying exons of both known and novel genes. (C) 1999 Academic Press., ACADEMIC PRESS INC
Genomics, 1999

Mutations of the Fanconi anemia group A gene(FAA)in Japanese patients
A Nakamura; S Matsuura; H Tauchi; R Hanada; H Ohashi; T Hasegawa; K Honda; M Masuno; K Imaizumi; K Sugita; T Ide; K Komatsu, Fanconi anemia (FA) is an autosomal recessive disorder characterized by pancytopenia, predisposition to cancers, and a diverse variety of congenital malformations. At least eight complementation groups, A through H, have been described. Recently, the FA-A gene (FAA) has been isolated, and a large number of distinct mutations reported in ethnically diverse FA-A patients. Here, we report on the mutation analysis of five FA patients by single-strand conformation polymorphism. Out of five patients, at least three were found to have mutations in the FAA gene. The first patient was a compound heterozygote with a l-bp deletion and a single-base substitution. The second patient had a heterozygous 2-bp deletion, which introduces a premature termination codon, and the third patient had a heterozygous splice donor site mutation in intron 27., SPRINGER-VERLAG TOKYO
Journal of Human Genetics, 1999

Cell cycle and LET dependence for radiation-induced mutation : A possible mechanism for reversed dose-rate effect.
Tauchi; H.; Endo; S.; Eguchi-Kasai; K.; Furusawa; Y.; Suzuki; M.; Matsuura; S.; Ando; K.; Nakamura; N.; Sawada; S.; Komatsu; K., Lead, A previous study of the mutagenic action of Cf-252 radiation in mouse L5178Y cells showed that the mutation frequency was higher when the dose was chronic rather than acute, which was in sharp contrast to the effects reported for gamma-rays (Nakamura and Sawada, 1988). A subsequent study using synchronized cells revealed that the cells at the G2/M stage were uniquely sensitive to mutation induction by Cf-252 radiation but not to gamma-rays (Tauchi et al., 1993). A log phase cell population was first subjected to conditioning gamma or Cf-252 radiation doses at different dose-rates. The cell cycle distribution of these cells was then observed, and they were then exposed to Cf-252 radiation, and the mutation rate was determined. The G2/M fraction increased by 3- to 4-fold when the conditioning doses (2 Gy of gamma or 1 Gy of Cf-252 radiation) were delivered chronically over 10 h, but only slightly when the same doses were delivered over a 1 h period or less. Subsequent Cf-252 irradiation gave higher mutation frequencies in the cells pre-irradiated with gamma-rays over a protracted period of time than in those exposed with the higher dose-rate gamma-rays. These results suggest that the radiation-induced G2 block could be at least partly (but not totally) responsible for this reverse dose-rate effect (Tauchi et al. 1996). Possible factors which cause the hyper-sensitivity of G2/ M cells to mutation induction by neutrons will be discussed., JAPAN RADIATION RESEARCH SOC
Journal of Radiation Ressearch, 1999

Expression of full-length NBS1 protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients.
A Ito; H Tauchi; J Kobayashi; K Morishima; A Nakamura; Y Hirokawa; S Matsuura; K Ito; K Komatsu, Cells from Nijmegen breakage syndrome (NBS) display multiple phenotypes, such as chromosomal instability, hypersensitivity to cell killing from ionizing radiation, and possibly abnormal cell cycle checkpoints. NBS1, a gene mutated in NBS patients, appears to encode a possible repair protein, which could form the foci of a sensor-like molecular complex capable of detecting DNA double strand breaks, however, it has no kinase domain for signaling DNA damage. Here, we report that the stable expression of NBS1 cDNA in NBS cells after transfection results in the complete restoration of foci formation in the nucleus, and in normal cell survival after irradiation. The prolonged G2 block observed after irradiation was also abolished by expression of NBS1, providing additional confirmation that the G2 checkpoint is abrogated in NBS cells. These results suggest that a defective NBS1 protein could be the sole cause of the NBS phenotype, and that NBS1 likely interacts with another protein(s) to produce the entire range of NBS phenotypic expression. (C) 1999 Academic Press., ACADEMIC PRESS INC
Biochemical and Biophysical Research Communications, 1999

Radiation-induced teratogenicity and embryo lethality in the scid mice.
SHOJI Shuneki; KOMATSU Kenshi; MATSUURA Shinya; TAUCHI Hiroshi; ENDO Satoru; ISHIMURA Yoshimasa; UESAKA Tosihiro; KATOH Osamu; WATANABE Hiromitsu, The Japan Radiation Research Society
Journal of radiation research, Dec. 1998

The relationship between NBS1 and cell death induced by ɤ-ray irradiation in lymphoblastoid
FUKAMI-KOBAYASHI Junya; FUJITA Kazushi; TAUCHI Hiroshi; MATSUURA Shinya; KOMATSU Kenshi; TANIMOTO Keiji, The Japan Radiation Research Society
Journal of radiation research, Dec. 1998

Nijmegen breakage syndrome : Sequence analysis of an 800-kb genomic region on chromosome 8q21.
TAUCHI Hiroshi; MATSUURA Shinya; MORISHIMA Kenichi; NAKAMURA Asako; SAKAMATO Shuichi; Kondo Noriko; ISOMURA Minoru; NAKAMURA Yusuke; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1998

Positional cloning of the gene for Nijmegen breakage syndrome
MATSUURA Shinya; TAUCHI Hiroshi; NAKAMURA Asako; KONDO Noriko; SAKAMOTO Shuichi; OSHIMURA Mitsuo; ISOMURA Minoru; NAKAMURA Yusuke; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1998

Nijmegen breakage syndrome : Analysis of an 800-kb genomic sequence
Tauchi H; Matsuura S; Morishima K; Nakamura A; Isomura M; Nakamura Y; Komatsu K
日本分子生物学会年会プログラム・講演要旨集, 01 Dec. 1998

Cloning of the NBS1 geng for Nijmegen breakage syndrome
Matsuura S; Tauchi H; Nakamura A; Kondo N; Sakamoto S; Oshimura M; Isomura M; Nakamura Y; Komatsu K
日本分子生物学会年会プログラム・講演要旨集, 01 Dec. 1998

マウスL5178Y細胞におけるHPRT欠損突然変異のLETおよび細胞周期依存性　　　　　　　　　　　　　　　
田内広; 遠藤暁; 松浦伸也; 笠井清美; 古澤佳也; 鈴木雅雄; 安藤興一; 澤田昭三; 小松賢志
広島医学, 01 Apr. 1998

A-T様電離放射線感受性を示すXRCC8相補性群の解析　　　　　　　　　　　　　　　
坂本修一; 中村麻子; 松浦伸也; 田内広; 遠藤暁; J.Thacher; 小松賢志
広島医学, 01 Apr. 1998

ナイミーヘン染色体不安定症候群(NBS)の家系分析によるマッピング　　　　　　　　　　　　　　　
近藤徳子; 松浦伸也; 遠藤暁; 田内広; C.Weemaes; 小松賢志
広島医学, 01 Apr. 1998

ナイミーヘン染色体不安定症候群：機能的相補性を応用したポジショナルクローニング　　　　　　　　　　　　　　　
松浦 伸也; 田内 広; 小松 賢志
放射線生物研究, 01 Apr. 1998

試験による染色体マッピング　　　　　　　　　　　　　　　
松浦伸也; 高見秀輝; 近藤徳子; 田内 広; 遠藤 暁; 押村光雄; C.Weemaes; 小松賢志
広島医学, 01 Apr. 1998

Comparative Genomic Hybridization(CGH)を用いた固形腫瘍における遺伝子増幅・欠失領域の検出　　　　　　　　　　　　　　　
松浦 伸也; 祖母井 努; 田内 広; 小松 賢志
放射線生物研究, 01 Apr. 1998

陽子線トラックストラクチャーコードの開発と陽子先W値の計算　　　　　　　　　　　　　　　
遠藤 暁; NIKJOO H; 星 正治; 高田 純; 上原 周三; 田内 広; 松浦 伸也; 小松 賢志; GOODHEAD D. T
放射線物理, 01 Apr. 1998

Radiation induction of p53 in cells from Nijmegen Breakage Syndrome and functional mapping of the underlying gene at 8q21.　　　　　　　　　　　　　　　
Komatsu K; Matsuura K; Matsuura S; Kondo N; Tauchi H; Oshimura M; Sweets D; Weemaes C
Disease Markers., 01 Apr. 1998

Estimation of Dose Absorbed Fraction for ¹³¹I-beta rays in Rat Thyroid
S. Endo; Y. Nitta; M. Ohtaki; J. Takada; V. Stepanenko; K. Komatsu; H. Tauchi; S. Matsuura; E. Iaskova; M. Hoshi
Journal of Radiation Research, 1998, [Reviewed]

Positional Cloning of the gene for Nijmegen Breakage Syndrome. (Jointly authored)
S Matsuura; H Tauchi; A Nakamura; N Kondo; S Sakamoto; S Endo; D Smeets; B Solder; BH Belohradsky; VMD Kaloustian; M Oshimura; M Isomura; Y Nakamura; K Komatsu, Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency and a high incidence of lymphoid cancers. Cells from NBS patients display chromosome instability, hypersensitivity to ionizing radiation and abnormal cell-cycle regulation after irradiation, all of which are characteristics shared with AT. Recently, the NBS locus was mapped at 8q21 by two independent approaches, complementation studies(1) and linkage analysis(2). Here, we report the positional cloning of the NBS gene, NBS1, from an 800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754 amino acids. The amino-terminal region of the protein shows weak homology to the yeast XRS2, MEK1, CDS1 and SPK1 proteins. The gene is expressed at high levels in the testes, suggesting that it might be involved in meiotic recombination. We detected the same 5-bp deletion in 13 individuals, and conclude that it is likely to be a founder mutation., NATURE AMERICA INC
Nature Genetics, 1998

AT-like induction of p53 in cells from Nijmegen Breakage Syndrome and functional mapping of the gene at 8q21. (Jointly authored)　　　　　　　　　　　　　　　
Disease Markers, 1998

Radiation induction of p53 in cells from Nijmegen breakage syndrome is defective but not similar to ataxia-telangiectasia. (Jointly authored)
K Matsuura; T Balmukhanov; H Tauchi; C Weemaes; D Smeets; K Chrzanowska; S Endou; S Matsuura; K Komatsu, p53-mediated signal transduction after exposure to ionizing radiation was examined in cells from patients with Nijmegen breakage syndrome (NBS), an autosomal recessive disease characterized by microcephaly, immunodeficiency, predisposition to malignancy, and a high sensitivity to ionizing radiation. NBS cells accumulated p53 protein in a dose-dependent fashion, with a peak level 2 hrs after irradiation with 5 Gy. However, the maximal level of p53 protein in NBS cells was constantly lower than in normal cells. Moreover, this attenuation of p53 induction was confirmed by decreased levels of p21(WAF1) protein, which is transcriptionally regulated by p53 protein. This defective induction of p53 protein in NBS is similar to that in ataxia-telangiectasia (AT), although the induced levels of p53 protein in NBS appeared to be the intermediate between normal cells and AT cells. This moderate p53 induction in NBS cells is consistent with the relatively mild radiation sensitivity and the abnormal cell cycle regulation post-irradiation, as present in NBS, Furthermore, all NBS cell lines used here exhibited time courses of p53 induction similar to normal cells, which is in contrast with p53 induction in AT cells, where the maximum induction shows a delay of approximately 2 hrs compared with normal cells. These evidences suggest a different function of each gene product in an upstream p53 response to radiation-induced DNA damage. (C) 1998 Academic Press., ACADEMIC PRESS INC
Biochemical and Biophysical Research Communications, 1998

Mutation Analysis of the Fanconi Anemia Genes in Japanese Patients
NAKAMURA Asako; MATSUURA Shinya; TAUCHI Hiroshi; HANADA Ryoji; OHASHI Hirofumi; HASEGAWA Tomonobu; HONDA Koujiro; MASUNO Mitsuo; IMAIZUMI Kiyoshi; SUGITA Katsuo; ENDO Satoru; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1997

Genetic Mapping of Nijmegen Breakage Syndrome using Functional Complementation Assays and Homozygosity Mapping
KONDO Noriko; MATSUURA Shinya; TAUCHI Hiroshi; SAKAMOTO Shuichi; NAKAMURA Asako; ENDO Satoru; OSHIMURA Mitsuo; WEEMAES Corry; SMEETS Dominique; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1997

Haplotype Analysis of Nijmegen Breakage Syndrome and Construction of Physical Map of Candidate Region.
MATSUURA Shinya; TAUCHI Hiroshi; KONDO Noriko; SAKAMOTO Shuichi; NAKAMURA Asako; ENDO Satoru; OSHIMURA Mitsuo; WEEMAES Corry; SMEETS Dominique; Concannon Patrick; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1997

Complementation Assay between Radiation-Sensitive irs2 Mutant and Ataxia-Telangiectasia Cell
SAKAMOTO Shuichi; NAKAMURA Asako; MATSUURA Shinya; TAUCHI Hiroshi; ENDO Satoru; OSHIMURA Mitsuo; THACKER John; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1997

Cell cycle and LET dependence for 6-thioguanine-resistant mutation induced by heavy ion beam in mouse L5178Y cells
Tauchi H; Eguchi -Kasai K; Matsura S; Endo S; Furusawa Y; Suzuki M; Ando K; Sawada S; Komatsu K, The Japan Radiation Research Society
Journal of radiation research, Dec. 1997

Complementation study and genetic mapping of nijmegen breakage syndrome　　　　　　　　　　　　　　　
S. Matsuura; H. Takami; N. Kondo; H. Tauchi; S. Endo; K. Komatsu; M. Oshimura; L. Weemaes
Japanese Journal of Human Genetics, 1997, [Reviewed]

Inhibitory action of (-)-epigallocatechin gallate on radiation-induced mouse oncogenic transformation.
K Komatsu; H Tauchi; N Yano; S Endo; S Matsuura; S Shoji, The anticarcinogenic activity of a major component of green tea, (-) epigallocatechin gallate (EGCg) was examined by using the radiation-induced oncogenic transformation in C3H10T1/2 cells. EGCg substantially suppressed the radiation-induced transformation so that the transformation frequency with 15 mu M of ECCg was reduced nearly to spontaneous levels. This effect of EGCg was in a dose-dependent manner and significant suppression of transformation was observed even in treatment of cells with 5 mu M of EGCg concentration where the cytotoxicity was mild, The inhibitory effect of EGCg was maximal when it was present during the entire incubation period. However, neither treatment Drier to nor concurrent with radiation was effective, suggesting that EGCg action is mainly involved in the promotional stage of C3H10T1/2 cell transformation. (C) 1997 Elsevier Science Ireland Ltd., ELSEVIER SCI IRELAND LTD
Cancer Letters, 1997

Genetic mapping using microcell-mediated chromosome transfer suggests a locus for Nijmegen Breakage Syndrome at chromosome 8q21-24. (Jointly authored)
S Matsuura; C Weemaes; D Smeets; H Takami; N Kondo; S Sakamoto; N Yano; A Nakamura; H Tauchi; S Endo; M Oshimura; K Komatsu, Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder characterized by microcephaly, short stature, immunodeficiency, and a high incidence of cancer. Cultured cells from NBS show chromosome instability, an increased sensitivity to radiation-induced cell killing, and an abnormal cell-cycle regulation after irradiation. Hitherto, patients with NBS have been divided into the two complementation groups V1 and V2, on the basis of restoration of radioresistant DNA synthesis, suggesting that each group arises from a different gene, However, the presence of genetic heterogeneity in NBS has been considered to be controversial. To localize the NBS gene, we have performed functional complementation assays using somatic cell fusion between NBS-V1 and NBS-V2 cells, on the basis of hyper-radiosensitivity, and then have performed a genomewide search for the NBS locus, using microcell-mediated chromosome transfer followed by complementation assays based on radiosensitivity, We found that radiation resistance was not restored in the fused NBS-V1 and NBS-V2 cells and that only human chromosome 8 complements the sensitivity to ionizing radiation, in NBS cell lines. In complementation assays performed after the transfer of a reduced chromosome, merely the long arm of chromosome 8 was sufficient for restoring the defect. Our results strongly suggest that NBS is a homogeneous disorder and that the gene for NBS is located at 8q21-24., UNIV CHICAGO PRESS
American Journal of Human Genetics, 1997

The Genetic Homogeneity of Nijmegen Breakage Syndrome V1 and V2.
MATSUURA Shinya; TAKAMI Hideki; KONDO Noriko; TAUCHI Hiroshi; ENDO Satoru; OSHIMURA Mitsuo; WEEMAES C; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1996

Radiation-induced HPRT mutation of a radiation sensitive hamster cell line irs1SF
YANO Nozomi; KONDO Noriko; MATSUURA Shinya; ENDO Satoru; TAUCHI Hiroshi; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1996

ハムスター電離放射線感受性細胞irs2とA-Tおよびそのバリアントとの遺伝的相補性
坂本修一; 松浦伸也; 田内 広; 遠藤; 暁; 城; 多恵子; THACKER J; 小松賢志
日本分子生物学会年会プログラム・講演要旨集, 01 Aug. 1996, [Reviewed]

ナイミーヘン染色体不安定症候群(NBS)線維芽細胞株の樹立と遺伝的均一性　　　　　　　　　　　　　　　
高見秀輝; 松浦伸也; 遠藤暁; 田内広; Weemaes C; 小松賢志
長崎医学会雑誌, 01 Apr. 1996

放射線高感受性マウスscid諸形質のヒト染色体8qll領域遺伝子による回復　　　　　　　　　　　　　　　
小松賢志; 田内広; 松浦伸也; 遠藤暁; 島崎達也; 奥村寛; 寺岡弘文
広島医学, 01 Apr. 1996

ハムスター放射線高感受性相補群XRCC3の原因遺伝子と機能　　　　　　　　　　　　　　　
矢野希; 松浦伸也; 遠藤暁; 田内広; 小松賢志
長崎医学会雑誌, 01 Apr. 1996, [Reviewed]

Establishment of new cell lines from patients with Nijmegen Breakage Syndrome and the genetic complementation group
KOMATSU Kenshi; MATSUURA Shinya; TAKAMI Hideki; TAUCHI Hiroshi; ENDO Satoru; OSHIMURA Mitsuo
Tissue culture research communications : the journal of experimental & applied cell culture research, 31 Mar. 1996

Accumulation of cells at G(2)/M stage by low dose-rate irradiation renders the cell population more susceptible to the subsequent induction of 6-thioguanine-resistant mutations by Cf-252 fission neutrons.
H Tauchi; N Nakamura; K Komatsu; S Sawada, A previous study on mutagenesis by Cf-252 radiation in mouse L5178Y cells showed that the frequency was higher when the dose was delivered chronically, which was in sharp contrast to the results by gamma-rays (Nakamura and Sawada, 1988). A subsequent study using synchronized cells revealed that the cells at G(2)/M stage were uniquely sensitive to mutation induction by Cf-252 radiation but not so by gamma-rays (Tauchi et al, 1993). We carried out the present study to test the possibility that radiation-induced G(2) block may be a major determinant of the inverse dose-rate effect following chronic Cf-252 radiation.
Growing cell population was first subjected to conditioning gamma or Cf-252 radiation with different dose-rates, followed by cell cycle distribution analysis and Cf-252 mutagenesis. We found that G(2)/M fraction increased by 3- to 4-fold when the conditioning doses (2 Gy of gamma or 1 Gy of Cf-252 radiation) were delivered chronically over 10 hours but only slightly so when the same doses were delivered for 1 hour or less. Subsequent Cf-252 irradiation gave higher mutation frequencies in the cells pre-irradiated with gamma-rays over a protracted period of time than in those with higher dose-rate gamma-rays. These results suggest that radiation-induced G(2) block would be at least partly (but can not be totally) responsible for the inverse dose-rate effect., JAPAN RADIATION RESEARCH SOC
JOURNAL OF RADIATION RESEARCH, Mar. 1996

The gene for Nijmegen Breakage Syndrome (V2) is not located on chromosome 11.
K Komatsu; S Matsuura; H Tauchi; S Endo; S Kodama; D Smeets; C Weemaes; M Oshimura, UNIV CHICAGO PRESS
American Journal of Human Genetics, 1996

DNA-dependent protein kinase restores mouse scid mutation
TAUCHI Hiroshi; MATSUURA Shinya; ENDO Satoru; TERAOKA Hirofumi; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1995

Genetic heterogeneity of ataxia-telangiectasia-like hamster mutant irs2 with Nijmegen breakage syndrome.
SAKAMOTO Shuichi; KOMATSU Kenshi; TAUCHI Hiroshi; MATSUURA Shinya; ENDO Satoru; J. THACKER, The Japan Radiation Research Society
Journal of radiation research, Dec. 1995

The genetic complementation assay of Nijmegen breakage syndrome witit ataxia telangiectasia on the basis of radiation sensitivity to cell killing.
TAKAMI Hideki; MATSUURA Shinya; TAUCHI Hiroshi; ENDO Satoru; KODAMA Seiji; C. WEEMAES; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1995

Inhibition of radiation-induced oncogenic transformation in C3H10T1/2 cells by green tea component, (-)-epigallocatechin gal late.
YANO Nozomi; TAUCHI Hiroshi; MATSUURA Shinya; ENDO Satoru; KOMATSU Kenshi, The Japan Radiation Research Society
Journal of radiation research, Dec. 1995

Neutron Generator at Hiroshima University for Use in Radiobiology Study
S. Endo; M. Hoshi; H. Tauchi; S. Takeoka; K. Kitagawa; S. Suga; N. Maeda; K. Komatsu; S. Sawada; K. Takeyama; S. Sakamoto; M. Omura; E. Iwamoto, A neutron generator (HIRRAC) for use in radiobiology study has been constructed at the Research Institute for Radiation Biology and Medicine, Hiroshima University (RIRBM). Monoenergetic neutrons of which energy is less than 1.3 MeV are generated by the 7Li(p,n)7 Be reaction at proton energies up to 3 MeV. The protons are accelerated by a Schenkel-type-accelerator and are bombared onto the 7Li-target, An apparatus for the irradiation of biological material such as mice, cultured cells and so on, was designed and will be manufactured. Neutron and gamma-ray dose rates were measured by paired (TE-TE and C-CO2) ionization chambers. Contamination of the gamma ray was less than about 6% when using 10-μm-thick 7Li as a target. Maximum dose rates for the tissue equivalent materials was 40 cGy/min at a distance of 10 cm from the target. Energy distributions of the obtained neutrons have been measured by a 3He-gas proportional counter. The monoenergetic neutrons within an energy region from 0.1 to 1.3 MeV produced by thin 7Li or 7LiF targets had a small energy spread of about 50keV (1 σ width of gaussian). The energy spread of neutrons was about 10% or less at an incident proton energy of 2.3 MeV. We found that HIRRAC produces small energy spread neutrons and at sufficient dose rates for use in radiobiology studies. © 1995, Journal of Radiation Research Editorial Committee. All rights reserved.
Journal of Radiation Research, 1995

Induction of somatic mutation and neoplastic transformation by neutrons : Reversed does - rate effect.　　　　　　　　　　　　　　　
Radiological Sciences, 1995

Expression of vascular endothelial growth factor (VEGF) receptor gene, KDR, in hematopoietic cells and inhibitory effect of VEGF on apoptotic cell death caused by ionizing radiation.
O KATOH; H TAUCHI; K KAWAISHI; A KIMURA; Y SATOW, Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we demonstrated the expression of the KDR gene transcript, which encodes a cell surface receptor for VEGF, in normal human hematopoietic stem cells, megakaryocytes, and platelets as well as in human leukemia cell lines, HEL and CMK86. Moreover, we showed the expression of VEGF gene transcript in these normal fresh cells and cell lines. To elucidate biological functions of VEGF on hematopoiesis, we determined whether this growth factor has mitogenic activity to hematopoietic cells or the ability to suppress apoptotic cell death. The liquid culture and colony-formation assay revealed that VEGF suppressed apoptotic cell death of both CMK86 cells and normal hematopoietic stem cells caused by gamma-ray irradiation, although mitogenic activity of VEGF was not detected. The ability of VEGF to suppress apoptotic cell death was independent of the change of cell cycle distribution. These data suggest that VEGF may play an important role in survival or maintenance of hematopoietic stem cells due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation and that VEGF may give leukemia cells some abilities of resistance against radiotherapy in an autocrine or paracrine manner., AMER ASSOC CANCER RESEARCH
Cancer Research, 1995

Suppressive effect of miso extract on radiation-induced in vitro carcinogenesis　　　　　　　　　　　　　　　
Journal of Hiroshima Medical Association, 1994

Analysis of mitotic cell death caused by radiation in mouse leukaemia L5178Y cells : apoptosis is the ultimate form of cell death following mitotic failure
H TAUCHI; S SAWADA, The appearance of various abnormal cells after irradiation was investigated in growing mouse leukaemia L5178Y cells. Morphologically defined apoptotic cells started to emerge at 10h after irradiation and the frequency reached a peak at around 48h being similar to the frequency of other abnormal cells, i.e. micronucleated, multinucleated and giant cells. Necrotic cells were rarely seen. The frequency of apoptosis and other abnormal cells depended on the radiation dose. The typical DNA ladder pattern for apoptosis was observed in the agarose gel electrophoretic analysis of the cells at 24-96h postirradiation. A decline in the frequency of apoptotic cells occurred with longer incubation, which was associated with a sharp increase in cloning efficiency. Changes in the growth rate of the irradiated cell population during the postirradiation period could be reasonably well described by a simple model using the frequencies of apoptosis and other abnormal cells. The results suggest that apoptosis is the ultimate form of cell death via mitotic failure caused by relatively small doses of radiation in L5178Y cells., TAYLOR & FRANCIS LTD
International Journal of Radiation Biology, 1994

CELL-CYCLE DEPENDENCE FOR THE INDUCTION OF 6-THIOGUANINE-RESISTANT MUTATIONS - G-2/M STAGE IS DISTINCTIVELY SENSITIVE TO CF-252 NEUTRONS BUT NOT TO CO-60 GAMMA-RAYS
H TAUCHI; N NAKAMURA; S SAWADA, Cell cycle dependence for the induction of 6-thioguanine-resistant mutation was investigated using synchronized mouse L5178Y cells after exposure to 4 Gy to Co-60 gamma-rays or 1Gy of Cf-252 radiation (fission neutrons). Maximal mutation frequency was observed immediately after release from colcemid block (G2/M phase) after Cf-252 radiation, whereas it was 1 h after the release (G1 phase) after Co-60 gamma-rays. When the mutation frequency was plotted against the surviving fraction, a general correlation was observed between the two parameters except for G2/M and G1 phases which were more mutable per lethal event for Cf-252 and Co-60 radiations, respectively., TAYLOR & FRANCIS LTD
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, Apr. 1993

Suppression of gamma-and neutron-induced neoplastic transformation by ascorbic acid in Balb/c 3T3 cells
H TAUCHI; S SAWADA, The effects of ascorbic acid on the neoplastic transformation induced by Co-60 gamma-rays or Cf-252 fission neutrons were studied. The transformation induced by each of the radiations was markedly suppressed when ascorbic acid was added daily to the culture medium during the first 8 days of the post-irradiation period. If ascorbic acid was added for a total of 8 days as mentioned above, but with 1 day interruption in the middle, the suppression of transformation was decreased. Ascorbic acid also suppressed the promotion of radiation transformation by 12-0-tet-radecanoylphorbol-13-acetate (TPA) when both chemicals were added to the medium together. However, promotion of radiation transformation by TPA was observed if both the chemicals were added sequentially during the post-irradiation period, i.e. ascorbic acid for the first 7 days followed by TPA. These results suggest that continuous administration of ascorbic acid for a certain number of days is needed to suppress the radiation transformation, and also suggest that it acts on the promotion stage of transformation., TAYLOR & FRANCIS LTD
International Journal of Radiation Biology, 1993

Effect of TPA, okadaic acid and 1α, 25-dihydroxyvitamin D₃ on neoplastic transformation induced by ⁶⁰Co gamma-rays of ²⁵²Cf fission neutrons in Balb/c 3T3 cells
H TAUCHI; T ENOMOTO; S SAWADA, The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), 1-alpha,25-dihydroxyvitamin D3 [1-alpha,25(OH)2D3] and okadaic acid were individually examined on the neoplastic transformation of Balb/c 3T3 cells which were exposed to either Co-60 gamma-rays or Cf-252 fission neutrons. The addition of 1-alpha, 25(OH)2D3, or TPA, enhanced the transformation induced by gamma-rays or low doses of fission neutrons. No enhancement was observed by the addition of okadaic acid except at toxic concentrations (5 ng/ml) and with higher doses of radiation. Moreover, the enhancement of transformation by either 1-alpha, 25(OH)2D3 or TPA decreased as the radiation dose was increased. The enhancement ratio, calculated by least-square analysis from 0 Gy to 1 Gy, was greater for 1-alpha, 25(OH)2D3 than for TPA, and also greater for gamma-ray irradiation than for neutron irradiation. These results suggest that the promotion of radiation-induced transformation depends on the level of the initial damage caused by radiation, and that the differences in the enhancement properties of different chemicals may be due to different individual triggering mechanisms involved in the transformation process., TAYLOR & FRANCIS LTD
International Journal of Radiation Biology, 1992

低エネルギー中性子による細胞癌化　　　　　　　　　　　　　　　
広島医学, 1992

Induction of neoplastic transformation by low energy fission neutrons in Balb/c 3T3 cells　　　　　　　　　　　　　　　
Journal of Hiroshima Medical Association, 1992

Deficiency of a 90-kDa protein in S-150 fraction isolated from radiation sensitive mutants of mouse leukemia cells　　　　　　　　　　　　　　　
Korean Biochemical Journal, 1991

Production of carbon monoxide from aromatic amino acids by ┣DBMorganella(/)-┫DB ┣DBmorganii(/)-┫DB
S HINO; H TAUCHI, SPRINGER VERLAG
Archives of Microbiology, 1987

A history and perspectives of tritium biology in Japan　　　　　　　　　　　　　　　
Hiroshi Tauchi
ATOMOS 日本原子力学会誌, Nov. 2024, [Reviewed], [Invited]
Lead

トリチウムの生体影響に関するエビデンス　　　　　　　　　　　　　　　
田内 広
日本放射線技術学会 放射線防護部会誌, 13 Apr. 2023, [Invited]

トリチウム生体影響研究の現状とこれから ―UNSCEAR 2016 を越えて―　　　　　　　　　　　　　　　
増田 毅、長島明輝、田内 広
放射線生物研究, Apr. 2023, [Reviewed]

放射線の生体影響 −基礎研究データからー　　　　　　　　　　　　　　　
田内 広
大阪大学医学部 学友会会誌, Dec. 2019, [Invited]

放射線感受性の遺伝的個人差を規定する候補素因としてのNBS1遺伝子I171V多型の逆遺伝学的解析
冨岡啓太; 冨岡啓太; 阿久津シルビア夏子; 柳原啓見; 田内広; 山本卓; 小林正夫; 工藤美樹; 宮本達雄; 松浦伸也
日本分子生物学会年会プログラム・要旨集(Web), 2019

Exploration of genetic basis underlying individual differences in radiosensitivity within human populations using genome editing technology
Tatsuo Miyamoto; Silvia Natsuko Akutsu; Hiroshi Tauchi; Yoshiki Kudo; Satoshi Tashiro; Takashi Yamamoto; Shinya Matsuura
Journal of Radiation Research, 01 Apr. 2018, [Reviewed], [Invited]

ゲノム編集技術を用いたNBS1I171Vノックインマウスの作製
宮本達雄; 阿久津シルビア夏子; 田内広; 松浦伸也
日本放射線影響学会大会抄録(Web), 2018

Biological Effects of Tritium from the Cellular and Molecular Aspects
TACHIBANA Akira; KOBAYASHI Junya; TAUCHI Hiroshi
プラズマ・核融合学会誌 = Journal of plasma and fusion research, 25 Apr. 2012

RNF20-dependent H2B ubiquitination modulates repair of DNA double-strand breaks by homologous recombination.　　　　　　　　　　　　　　　
kihiro Kato; Kyosuke Nakamura; Junya Kobayashi; Hiromi Yanagihara; Shuichi Sakamoto; Hiroshi Tauchi; Satoshi Tashiro; Lee Zou; Kenshi Komatsu
日本放射線影響学会第55 回大会，2012 年9 月， 仙台, 2012, [Reviewed]

低線量放射線の生物影響とトリチウム研究　　　　　　　　　　　　　　　
田内 広; 馬田敏幸; 立花 章
プラズマ核融合学会誌, 2012, [Reviewed], [Invited]
Lead

放射線による細胞死を考える(その2) 治療戦略に向けて DNA損傷修復機構の治療戦略への応用　　　　　　　　　　　　　　　
田内 広; 船生 悠美; 大原 麻希; 坂田 耕一; 染谷 正則; 関 良太; 飯島 健太; 小松 賢志; 晴山 雅人
日本放射線影響学会大会講演要旨集, Nov. 2011

The roles of NBS1 in responses to radiation- and UV-induced DNA damage　　　　　　　　　　　　　　　
Kenshi Komatsu; Kyosuke Nalcamura; Akihiro Kato; Junya Kobayashi; Hiromi Yanagihara; Douglas V.N.P; Oliveira; Mikio Shimada; Satoshi Tashiro; Shinya Matsuura; Toshio Mori; Hiroshi Tauchi
The Sugahara Memorial International Symposium, Kyoto, January 25 ， 2011( 招待講演), 2011, [Reviewed]

DNA double-strand break repair via gene conversion is dependent on cell cycle.　　　　　　　　　　　　　　　
Kokuta Tetsuya; Ai Techigawara; naoki Hasegawa; Minora Takata; Kenshi Komatsu; Hiroshi Tauchi
第34 回日本分子生物学会年会 2011 年12 月 横浜, 2011, [Reviewed]

ナイミーヘン症候群における二本鎖DNA切断修復の異常　　　　　　　　　　　　　　　
Hiroshi Tauchi
Journal of Gastrointestinal Research, 01 Apr. 2010, [Invited]

「DNA 修復におけるRNF20 の役割」
中村恭介; 加藤晃弘; 坂本修一; 小林純也; 田内広; 田代聡; 小松賢志
日本放射線影響学会第51 回大会 2008 年11 月 北九州市, 2008, [Reviewed]

Current topics in DNA double-strand break repair
Kobayashi; J.; Iwabuchi; K.; Miyagawa; K.; Sonoda; E.; Suzuki; K.; Takata; M.; Tauchi; H.
Journal of Radiation Research, 2008, [Reviewed], [Invited]
Corresponding

Dancing on damaged chromatin: Functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage
Iijima; K.; Ohara; M.; Seki; R.; Tauchi; H.
Journal of Radiation Research, 2008, [Reviewed], [Invited]
Corresponding

AT the broken DNA end −ATMとNBS1を中心としたDNA損傷応答経路−
関良太; 江原俊介; 田中彩; 片吉健史; 飯島健太; 田内 広
放射線生物研究, Dec. 2007, [Invited]
Corresponding

「DNA 二重鎖切 断修復におけるNBS1 、ATM の役割」　　　　　　　　　　　　　　　
小林純也; 坂本修一; 飯島健太; 森島賢一; 中村恭介; 松浦伸也; 田内広; 小松賢志
第30 回日本分子生物学会年会 2007 年12 月, 2007, [Reviewed]

DNA の二重鎖 切断損傷におけるNBSl とヒストンH2AX の役割
小林純也; 坂本修一; 飯島健太; 森島賢一; 中村恭介; 松浦伸也; 田内広; 小松賢志
日本放射線影響学会第50 回大会2007 年11月, 2007, [Reviewed]

放射線被曝後に誘発されるTopBP1フォーカスとDNA修復機構
森島賢一; 小林純也; 坂本修一; 泉秀樹; 須田哲司; 松本祥幸; 田内広; 小松賢志; 松浦伸也
原子爆弾後障害研究会特集号, 2006

DNA 修復因子hMREll の相同組換えにおける役割
島田幹男; 小林純也; 田内広; 小松賢志
日本放射 線影響学会第49 回大会、北海道、2006 年9 月, 2006, [Reviewed]

DNA 損傷修復遺伝子NBS1 によるアポトーシス制御　　　　　　　　　　　　　　　
田内広; 小林純也; 小松賢志; 松浦伸也
第65 回二本癌学会学術総会、神奈川県、2006 年9 月, 2006, [Reviewed]

DNA 二重鎖切断修 復におけるTopBPl フォーカスの意義　　　　　　　　　　　　　　　
森島賢一; 小林純也; 坂本修一; 泉英樹; 須田哲司; 田内広; 小松賢志; 松浦伸也
第65 回二本癌学会学術総会、神奈川県、2006 年9 月, 2006, [Reviewed]

NBS1 によるATM 非依存的MRE11 局在を介した相同組換え修復の調節
中村恭介; 坂本修一; 飯島健太; 望月大輔; 勅使河原計介; 小林純也; 松浦伸也; 田内広; 小松賢志
日本放射線影響学会第49 回大会、北海道、2006 年9 月, 2006, [Reviewed]

NBS1 による放 射線誘発アポトーシスの制御
飯島健太; 村中千寿子; 小林純也; 坂本修一; 小松賢志; 松浦伸也; 一政祐輔; 田内広
日本放射線影響学会第49 回大会、北海道、2006 年9 月, 2006, [Reviewed]

DNA しゅうふくにおけるメ ディエータータンパクTopBP 1 の役割
森島賢一; 小林純也; 坂本修一; 須田哲司; 田内広; 小松賢志; 松浦伸也
日本放射線影響学会第49 回大会、北海道、2006 年9 月, 2006, [Reviewed]

ATM 依存性DNA 損傷応答の活性化におけるy-H2AX とNBS1 との協調的役割　　　　　　　　　　　　　　　
小林純也; 田内広; 森島賢一; 松浦伸也; 小松賢志
第65 回二本癌学会学術総会、神奈川県、2006 年9 月, 2006, [Reviewed]

「高LET 重イオン線による DNA 損傷に対するNBS1 の応答」　　　　　　　　　　　　　　　
富田雅典; 松本義久; 青木瑞穂; 古澤佳也; 矢野安重; 酒井一夫; 細井義夫; 小松賢志; 田内広
日本放射線影響学会第48 回大会、平成1 7 年11 月、広島市, 2005, [Reviewed]

「PCS 症候群7 家 系の遺伝子解析」　　　　　　　　　　　　　　　
松本祥幸; 泉秀樹; 森島賢一; 小林純也; 田内広; 小松賢志; 池内達郎; 梶井正; 松浦伸也
日本放射線影響学会第48 回大会、平成17 年11 月、広島市, 2005, [Reviewed]

「NBS1 が制御する損傷チェックポイントならびにアポトー シス経路」　　　　　　　　　　　　　　　
田内広; 小林純也; 坂本修一; 松浦伸也; 小松賢志
第64 回日本癌学会学術総会、平成17 年9 月、札幌市, 2005, [Reviewed]

「高発がん性を示す染色分 対早期解離(PCS) 症候群:BUB IB遺伝子変異とその機能解析」　　　　　　　　　　　　　　　
松浦伸也; 森島賢一; 泉秀樹; 小林純也; 田内広; 小松賢志; 池内達郎; 梶井正
第64 回日本癌学会学術総会、平成17 年9 月、札幌市, 2005, [Reviewed]

「D S B の相同組換え修復におけるNB S 1 の作用機構の解析」　　　　　　　　　　　　　　　
坂本修一; 田内広; 飯島健太; 勅使河原計介; 中村恭介; 小林純也; 松浦伸也; 小松賢志
組換えワークショップ、平成16 年12 月、兵庫県, 2004, [Reviewed]

「NBS 1 に依存したアポトーシス誘発経路の解析」　　　　　　　　　　　　　　　
望月大介; 尾形裕美; 村中千寿子; 小林純也; 坂本修一; 小松賢志; 一政祐輔; 窪田宣夫; 田内広
第47 回日本放射線影響学会、平成16 年 11 月、長崎県, 2004, [Reviewed]

「突然変異好感度検出系を用いた高LET 放射線の低線量率降下解析」　　　　　　　　　　　　　　　
田内広; 岩田佳之; 屋良早香; 小柳陽子; 奥村志乃; 和久弘幸; 笠井清美; 吉沢佳也; 小松賢志
第47 回日本放射線影響学会、 平成16 年11 月、長崎県, 2004, [Reviewed]

「NBS 1 によるDNA 二重鎖切断の修復とチェックポイント制御」　　　　　　　　　　　　　　　
Antoccia Antonio; 坂本修一; 松浦伸也; 小林純也; 田内広; 小松賢志
第27 回日本分子生物学会、平成16 年12 月、兵庫県, 2004, [Reviewed]

相同組換えを制御するNBS1タンパクにおける機能ドメイン解析　　　　　　　　　　　　　　　
飯島健太; 坂本修一; 小林純也; 松浦伸也; 小松 賢志; 田内広
第 27 回日本分子生物学会、平成16 年12 月、兵 庫県, 2004, [Reviewed]

放射 線高感受性を呈する日本人新規患者細胞の解析　　　　　　　　　　　　　　　
藤本浩子; 伊藤早織; 田内広; 小林純也; 山田雅 文; 小林邦彦; 松浦伸也; 小松賢志
第47 回日本放射線影響学会、平成16 年 11 月、長崎県, 2004, [Reviewed]

DNA 損傷認識におけるN BSI の機能について　　　　　　　　　　　　　　　
小林純也; 田内広; 坂本修一; 森島賢一; 松浦伸 也; 小松寶志
第63 回日本癌学会学術総会、平成 16 年9 月、福岡県．, 2004, [Reviewed]

DNA二重鎖切断修復の初期過程におけるNBS1とヒストンH2AXの機能　　　　　　　　　　　　　　　
小林 純也; 田内 広; 篠原 美紀; 松浦 伸也; 谷本 啓二; 小松 賢志
日本放射線影響学会大会講演要旨集, Oct. 2001

Developmental malformations and intrauterine deaths in gamma-ray-irradiated scid mouse embryos
S Shoji; H Watanabe; O Katoh; Y Masaoka; S Matsuura; H Tauchi; S Endo; K Komatsu
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, Jun. 1998

培養細胞を用いた放射線影響の研究　　　　　　　　　　　　　　　
広島大学原爆放射能医学研究所年報, 1991

放射線医科学の事典　　　　　　　　　　　　　　　
Contributor
朝倉書店, Dec. 2019
9784254301175

新版「放射線医科学」−生体と放射線・電磁波・超音波−　　　　　　　　　　　　　　　
Joint editor
医療科学社, Nov. 2016
9784860034818

本当のところを教えて！放射線のリスク　　　　　　　　　　　　　　　
日本放射線影響学会, Joint work
医療科学社, 22 Jan. 2015
9784860034542

「放射線医科学」−生体と放射線・電磁波・超音波−　　　　　　　　　　　　　　　
田内 広, Single work
学会出版センター, Mar. 2007

DNA損傷に対応する修復シグナルの概要．　　　　　　　　　　　　　　　
田内 広, Single work
キーワードで理解する「細胞周期イラストマップ」 羊土社, Feb. 2005

Suppresion of radiation-induced ┣DBin vitro(/)-┫DB carcinogenesis by ascorbic acid　　　　　　　　　　　　　　　
Radiation Carcinogenesis and its Control, 1993

食品中の放射性物質による内部被ばく　　　　　　　　　　　　　　　
田内 広
食の安全と安心フォーラム第28回「消費者のリスク認知バイアスを解消するための科学コミュニケーションとは」, 09 Mar. 2025, [Invited]

トリチウム内部被ばくは何が特殊なのか？　　　　　　　　　　　　　　　
田内 広
日本放射線影響学会第67回大会, 27 Sep. 2024, [Invited]

部位特異的DNA 二本鎖切断による突然変異誘発に対するDNA-PK キナーゼ活性阻害の影響　　　　　　　　　　　　　　　
今関桃花; 明道友希; 坂本裕貴; 佐藤圭汰; 飯島健太; 田内 広
日本放射線影響学会第67回大会, 25 Sep. 2024

DNA 二本鎖切断修復の経路選択における線量依存性が突然変異誘発に与える影響　　　　　　　　　　　　　　　
明道友希; 久野在世; 塩足敏士; 小松賢志; 田内 広
日本放射線影響学会第67回大会, 25 Sep. 2024

わが国におけるトリチウム生体影響研究の歴史と未解明の課題　　　　　　　　　　　　　　　
田内 広
アイソトープ・放射線研究発表会, 03 Jul. 2024, [Invited]

〔Major achievements〕A hyper-sensitive system for analysis of mutation induction by low dose or low dose-rate radiations: Comparison between HTO and gamma-rays　　　　　　　　　　　　　　　
Hiroshi TAUCHI
Biological Effects & Application of Radiation (BEAR2024), 15 Mar. 2024, BEAR2024 Organizing Committee, [Invited]
20240315, 20240317

ゲノム編集技術を用いた突然変異高感度検出系の改良　　　　　　　　　　　　　　　
明道友希、谷本早紀、長島明輝、坂本裕貴、坪田一希、宮本達雄、松浦伸也、田内 広
日本放射線影響学会第66回大会, 07 Nov. 2023, 一般社団法人 日本放射線影響学会
20231106, 20231108

Tritium biology in Japan: past and prospects for the future　　　　　　　　　　　　　　　
Hiroshi Tauchi; Masatoshi Suzuki; Tsuyoshi Masuda; Akira Tachibana
66th Annual Meeting of the Japanese Radiation Research Society, 06 Nov. 2023, Japanese Radiation Research Society, [Invited]
20231106, 20231108

Effect of PI3-kinase inhibitors on DNA double strand break repair pathways: An approach using a site specific DSB induction system　　　　　　　　　　　　　　　
Tomoki Myodo; Yuki Sakamoto; Honami Kobayashi; Kenta Iijima; Kenshi Komatsu; Shinya Matsuura; Hiroshi Tauchi
International Symposium on Natural and Artificial Radiation Exposures and Radiological Protection Studies (NARE2023), 20 Sep. 2023, NARE2023 Organising Committee
20230919, 20230922

Analysis of low-concentration tritiated water induced mutations using a hyper-sensitive assay system and understanding tritium disposition in the body using deuterium-labeled compounds　　　　　　　　　　　　　　　
Nagashima H; Komatsu K; Tauchi H
17th International Congress for Radiation Research (ICRR), Aug. 2023
20230827, 20230830

トリチウムの生体影響について：科学的な視点から　　　　　　　　　　　　　　　
田内 広
食のリスクコミュニケーション・フォーラム2023「消費者市民のリスクリテラシー向上につながるリスコミとは」、第２回トリチウム処理水のリスコミのあり方, 25 Jun. 2023, NPO法人 食の安全と安心を科学する会, [Invited]
20230625, 20230625

トリチウムの生体影響に関するエビデンス　　　　　　　　　　　　　　　
田内 広
第79回日本放射線技術学会総会学術大会, 14 Apr. 2023, 一般社団法人 日本ラジオロジー協会, [Invited]
20230413, 20230416

Analysis of factors which modulate DNA double strand break repair pathways　　　　　　　　　　　　　　　
明道友希、坂本裕貴、小林穂波、種田旭将、名倉莊一郎、飯島健太、小松賢志、松浦伸也、田内 広
日本放射線影響学会第65回大会, 15 Sep. 2022, 一般社団法人 日本放射線影響学会
20220915, 20220917

Dose and Dose-rate dependence of radiation-induced mutation: An approach using a hyper-sensitive cell system　　　　　　　　　　　　　　　
Nagashima H.; Hayashi Y.; Tanimoto S.; Shiraishi K.; Sakamoto Y.; Tauchi H.
The 6th International Symposium of the Network-type Joint Usage/ Research Center for Radiation Disaster Medical Science - Risk Communication in Radiation Disaster – During Crisis and Reconstruction -, 07 Feb. 2022, 放射線災害・医科学研究拠点, [Invited]
20220207, 20220207

ALPS処理水に含まれるトリチウムの生体影響　　　　　　　　　　　　　　　
田内 広
福島医学会学術研究集会シンポジウム「ALPS処理水を知る」, 19 Dec. 2021, 福島医学会, [Invited]
20211219

突然変異の高感度検出系における放射線誘発型変異の線量および線量率依存性解析　　　　　　　　　　　　　　　
田内 広
環境研セミナー, 05 Nov. 2021, （公財）環境科学技術研究所, [Invited]

Analysis of Dose and Dose-rate dependence of Radiation-Type mutation induced by tritiated water: An approach using a hyper-sensitive cell system.　　　　　　　　　　　　　　　
Nagashima H.; Hayashi Y.; Tanimoto S.; Shiraishi K.; Sakamoto Y.; Tauchi H.
Aomori (Online), 29 Sep. 2021, Institute of Environmental Science, [Invited]
20210927, 20210929

NBS1遺伝子 I171V 多型の放射線感受性に対する定量的評価　　　　　　　　　　　　　　　
Keita Tomioka1; Silvia Natsuko Akutsu; Hiromi Yanagihara; Hiroshi Tauchi; Takashi Yamamoto; Masao Kobayashi; Yoshiki Kudo; Tatsuo Miyamoto; Shinya Matsuura
日本放射線影響学会第62回大会, 15 Nov. 2019, 日本放射線影響学会

相同組換え修復の細胞周期依存性解析　　　　　　　　　　　　　　　
坂本 裕貴; 穀田 哲也; 勅使河原; 飯島 健太; 高田 穣; 小松 賢志; 田内 広
日本放射線影響学会第62回大会, 14 Nov. 2019, 日本放射線影響学会

高感度検出系を用いたトリチウム水による体細胞突然変異体の解析　　　　　　　　　　　　　　　
長島 明輝; 林 雄樹; 細江 一稀; 白石 久美子; 大川 沙織; 小松 賢志; 立花 章; 田内 広
日本放射線影響学会第62回大会, 14 Nov. 2019, 日本放射線影響学会

An approach for drug discovery targeting DNA double-strand break repair pathway　　　　　　　　　　　　　　　
Hiroshi Tauchi; Masaki Unno; Shinya Matsuura; Tatsuo Miyamoto; Keiji Suzuki
日本放射線影響学会第62回大会 シンポジウム, 16 Nov. 2019, 一般社団法人 日本放射線影響学会, [Invited]
201911, 201911

Analysis of somatic mutations induced by low-dose X-rays by using a hypersensitive system.　　　　　　　　　　　　　　　
Nagashima; H.; Hosoe; K.; Shiraishi; K.; Ohkawa; S.; Sakamoto; Y.; Komatsu; K.; Matsuura; S.; Tauchi; H.
The 3rd International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science, 13 Jan. 2019

低線量X 線が誘発する体細胞突然変異体の解析　　　　　　　　　　　　　　　
長島明輝; 細江一稀; 白石久美子; 大川沙織; 小松賢志; 立花 章; 田内 広
日本放射線影響学会第61回大会, 08 Nov. 2018, 日本放射線影響学会

相同組換え修復効率の細胞周期に依存した変化　　　　　　　　　　　　　　　
坂本裕貴; 穀田哲也; 勅使河原愛; 飯島健太; 高田 穣; 小松賢志; 田内 広
日本放射線影響学会第61回大会, 08 Nov. 2018, 日本放射線影響学会

Analysis of somatic mutations induced by low-dose X-rays: an approach using hypersensitive system.　　　　　　　　　　　　　　　
Nagashima; H.; Shiraishi; K.; Ohkawa; S.; Sakamoto; Y.; Komatsu; K.; Matsuura; S.; Tachibana; A.; Tauchi; H.
8th International Society of Radiation neurobiology Conference, 10 Feb. 2018

Effect of serum derived from the mice bred in enriched environment on DNA damage repair kinetics　　　　　　　　　　　　　　　
Sakamoto; Y.; Ueki; Y.; Kanuka; Y.; Takayama; Y.; Nakamura; A.J.; Nishimura; M.; Morioka; T.; Kakinuma; S.; Shimada; S.; Tauchi; H.
8th International Society of Radiation neurobiology Conference, 08 Feb. 2018

DNA二重鎖切断の相同組換え修復に対する損傷応答キナーゼ活性の役割　　　　　　　　　　　　　　　
田部井由依; 佐藤圭汰; 小摩木里奈; 大橋由佳; 小林穂波; 坂本敬祥; 布施谷清香; 坂本裕貴; 小松賢志; 田内 広
生命科学系学会合同年次大会（日本分子生物学会年会）, 07 Dec. 2017

茨城大学大学院の取り組み：量子線科学専攻・環境放射線科学コースにおける人材養成　　　　　　　　　　　　　　　
田内 広; 中村麻子; 立花 章
日本放射線影響学会第60回大会, 27 Oct. 2017, 一般社団法人 日本放射線影響学会, [Invited]

飼育環境の異なるマウス血清がDNA損傷修復に与える影響.　　　　　　　　　　　　　　　
高山侑里; 植木優斗; 坂本裕貴; 鹿糠佑斗; 中村麻子; 西村まゆみ; 森岡孝満; 柿沼志津子; 島田義也; 田内 広
日本放射線影響学会第60回大会, 27 Oct. 2017

低線量率のトリチウムβ線照射が誘発する体細胞突然変異　　　　　　　　　　　　　　　
長島明輝; 白石久美子; 大川沙織; 菅谷紘太; 小松賢志; 立花 章; 田内 広
日本放射線影響学会第60回大会, 27 Oct. 2017

Tritium Biology in Japan: A search for a new approach　　　　　　　　　　　　　　　
Tauchi; H.
2nd Asia-Pacific Symposium on Tritium Science, 07 Sep. 2017, [Invited]

DNA二重鎖切断が誘発する体細胞突然変異におけるNBS1機能の役割　　　　　　　　　　　　　　　
田内 広
第39回日本分子生物学会年会, 01 Dec. 2016

高感度検出系を用いた低線量・低線量率照射による体細胞突然変異の解析　　　　　　　　　　　　　　　
長島明輝; 白石久美子; 大川沙織; 菅谷紘太; 小松賢志; 立花 章; 田内 広
日本放射線影響学会第59回大会, 26 Oct. 2016

部位特異的DSBで誘発される体細胞突然変異における修復機構の役割　　　　　　　　　　　　　　　
小摩木里奈; 小林穂波; 坂本敬祥; 小林健太; 本田千明; 布施谷清香; 飯島健太; 小林純也; 小松賢志; 田内 広
日本放射線影響学会第59回大会, 26 Oct. 2016

部位特異的 DNA 二重鎖切断により誘発される 体細胞 突然変異の解析　　　　　　　　　　　　　　　
坂本敬祥; 小林穂波; 小林健太; 本田千明; 飯島健太; 小林純也; 小松賢志; 立花 章; 田内 広
日本放射線影響学会ワークショップ, 16 Oct. 2015, 日本放射線影響学会

細胞周期による相同組換え修復効率の変化　　　　　　　　　　　　　　　
坂本裕貴; 大川沙織; 穀田哲也; 勅使河原愛; 飯島健太; 高田 穣; 小松賢志; 田内 広
日本放射線影響学会ワークショップ, 16 Oct. 2015, 日本放射線影響学会

Function of NBS1 protein in the pathways responding to DNA double strand breaks induced by ionizing radiation.　　　　　　　　　　　　　　　
Tauchi; H.
The 12th International Workshop on Microbeam Probes of Cellular Radiation Response, 31 May 2015, [Invited]

Analysis of mutation spectrum induced by a site specific DNA double strand break　　　　　　　　　　　　　　　
Sakamoto; K.; Kobayashi; H.; Kobayashi; K.; Honda; C.; Iijima; K.; kobayashi; J.; Komatsu; K.; Tachiban; A.; Tauchi; H.
15th International Congress of Radiation Research (ICRR2015), 28 May 2015

Induction of somatic mutation by low dose radiation: an approach by using a hyper-sensitive assay system　　　　　　　　　　　　　　　
Tabei; Y.; Shiraishi; K.; Okawa; S.; Sugaya; K.; Komatsu; K.; Tauchi; H
15th International Congress of Radiation Research (ICRR2015), 27 May 2015

Cell cycle dependence of DNA double strand break repair by homology-directed repair　　　　　　　　　　　　　　　
Sakamoto; Y.; Okawa; S.; Kokuta; T.; Teshigahara; A.; Iijima; K.; Takata; M.; Komatsu; K.; Tauch; H.
5th International Congress of Radiation Research (ICRR2015), 27 May 2015

An experimental approach for analysis of biological effect of low dose radiation and factors affecting DSB repair fidelity　　　　　　　　　　　　　　　
Hiroshi Tauchi
30th RBC-NIRS International Symposium, 20 Feb. 2015, Radiation Biology Center, Kyoto University, [Invited]

細胞周期とNBS1機能がDNA二重鎖切断修復効率と精度に与える影響　　　　　　　　　　　　　　　
田内 広; 坂本裕貴; 穀田哲也; 大川沙織; 小林健太; 小林純也; 飯島健太; 小松賢志
第37回日本分子生物学会年会, 26 Nov. 2014, 日本分子生物学会

相同組換え修復能の阻害による放射線感受性の変化と突然変異誘発　　　　　　　　　　　　　　　
田内 広; 穀田哲也; 大川沙織; 坂本裕貴; 江原俊介; 船生悠美; 小林健太; 小林純也; 飯島健太; 小松賢志
日本放射線影響学会第57回大会, 02 Oct. 2014, 日本放射線影響学会, [Invited]

Modification of camptothecin sensitivity by PARP inhibitor in DNA double strand break repair deficient cell lines　　　　　　　　　　　　　　　
Ohara; M; Tanaka; A.; Isaka; S.; Tomatsu; S.; Takata. M.; Komatsu; K.; Tatibana; A.; Tauchi; H.
RIRBM International Symposium, 13 Feb. 2014, RIRBM, Hiroshima University

Effect of ATM kinase inhibitor on radiosensitivity of various DNA double strand break repair deficient cells.　　　　　　　　　　　　　　　
Sakamoto; Y.; Fukasaku; N.; Abe; H.; Tanaka; A.; Tomatsu; S.; Ohara; M.; Takata; M.; Komatsu; K.; Tachibana; A.; Tauchi; H
29th RBC-NIRS International Symposium, Nov. 2013, Kyoto University

DNA損傷修復関連タンパクによるアポトーシス制御の二面性　　　　　　　　　　　　　　　
田内 広; 大原麻希; 田中 彩; 飯島健太; 高田 穣; 小林純也; 小松賢志
日本放射線影響学会第56回大会 シンポジウム, 20 Oct. 2013, 日本放射線影響学会, [Invited]

DNA二重鎖切断修復欠損細胞におけるATM阻害の影響　　　　　　　　　　　　　　　
坂本裕貴; 深作直子; 阿部紘子; 田中 彩; 戸松静香; 大原麻希; 高田 穣; 小松賢志; 立花 章; 田内 広
日本放射線影響学会第56回大会, 18 Oct. 2013, 日本放射線影響学会

Kinetics of Radiation-Induced DNA Double Strand Break Rejoining in DNA Repair Deficient Cells　　　　　　　　　　　　　　　
Maki Ohara; Yuki Sakamoto; Junko Fukasaku; Kenshi Komatsu; Shinya Matsuura; Hiroshi Tauchi
RIRBM International Symposium, 21 Feb. 2013, 広島大学原爆放射線医科学研究所

高感度検出系を用いた放射線感受性修飾効果の解析　　　　　　　　　　　　　　　
田内 広; 江原俊介; 船生悠美; 大原麻希; 宮本智弘; 関 良太; 小松賢志; 立花 章
日本放射線影響学会第55回大会, Sep. 2012, 日本放射線影響学会, [Invited]

Functional Link Between Nbs1 and Ku70 in DNA Damage Response　　　　　　　　　　　　　　　
H. Tauchi; M. Ohara; H. Abe; A. Tanaka; K. Iijima; J. Kobayashi; K.Komatsu; S. Matsuura
広島大学原爆放射線医科学研究所国際シンポジウム, Mar. 2011, 広島大学原爆放射線医科学研究所

Assessment of biological effect of tritiated water by using hypersensitive system　　　　　　　　　　　　　　　
H. Tauchi; H. Imamura; M. Inoue; K. Komatsu; and A. Tachibana
9th International Conference on Tritium Science and Technology, Oct. 2010, [Invited]

Functional relationship between Nbs1 and Ku70 in cellular responses to DNA damage　　　　　　　　　　　　　　　
Hiroshi Tauchi; Maki Ohara; Aya Tanaka; Kenta Iijima; Hiroko Abe; Kenshi Komatsu; Junya Kobayashi
Annual Meeting of RadiationResearch Sciety, Sep. 2010, Radiation Research Sciety

Interaction Between NBS1 and Ku70 Regulates Apoptosis Induction by Radiation　　　　　　　　　　　　　　　
Kenta Iijima; Chizuko Muranaka; Junya Kobayashi; Shuichi Sakamoto; Kenshi Komatsu; Shinya Matsuura and Hiroshi Tauchi
International Workshop on DNA damage, Jun. 2008

NBS1 regulates DNA-damage induced apoptosis through Bax activation　　　　　　　　　　　　　　　
Kenta Iijima; Chizuko Muranaka; Junya Kobayashi; Shuichi Sakamoto; Kenshi Komatsu; and Hiroshi Tauchi
Ataxia-telangiectasia International Workshop, Apr. 2008

NBS1 regulates the induction of apoptosis following radiation damage to DNA　　　　　　　　　　　　　　　
Kenta Iijima; Chizuko Muranaka; Junya Kobayashi; Shuichi Sakamoto; Kenshi Komatsu and Hiroshi Tauchi
13th International Congress on Radiation Research, Jul. 2007, International Association of Radiation Research

NBS1 regulates DNA-damage induced apoptosis independent of p53　　　　　　　　　　　　　　　
Kenta Iijima; Chizuko Muranaka; Junya Kobayashi; Kenshi Komatsu; Shinya Matsuura; Yusuke Ichimasa
20th IUBMB International Congress of Biochemistry and Molecular Biology, Jun. 2006

Human NBS1 regulates homology directed DNA repair through its N-terminal conserved domain　　　　　　　　　　　　　　　
Hiroshi Tauchi
Benzon Symposium No.52, Cellular Responces to DNA damage, 24 Aug. 2005, Alphred Benzon Faundation

DNA repair pathways mediated by Nijmegen breakage syndrome protein, Nbs1　　　　　　　　　　　　　　　
Hiroshi Tauchi
5th Japan-France Workshop on Radiaobiology and Medical Imaging, Jun. 2004, [Invited]

Nbs1, an essential factor for DNA damage response in vertebrate cells　　　　　　　　　　　　　　　
Hiroshi Tauchi
Kyoto University COE International Symbosium, Dec. 2003, [Invited]

Essential role of Nbs1 in DNA repair and damage response　　　　　　　　　　　　　　　
Hiroshi Tauchi
12th International Congress of Radiation Research, Aug. 2003, [Invited]

Apr. 2023 - Present
茨城大学大学院理工学研究科

Apr. 2016 - Present
茨城大学大学院理工学研究科

Oct. 2001 - Present
茨城大学理学部

Apr. 2001 - Present
茨城大学理学部

Apr. 2001 - Present
茨城大学理学部

Apr. 2002 - Mar. 2016
茨城大学大学院理工学研究科

茨城北西看護専門学校

Clinical Microbiology　　　　　　　　　　　　　　　
茨城北西看護専門学校

1996 - Dec. 2018, 米国人類遺伝学会(American Society of Human Genetics)

1990, 日本植物学会

日本宇宙生物科学会

日本分子生物学会

日本癌学会

米国放射線影響学会(Radiation Research Society)

日本放射線影響学会

DNA修復細胞集団の再分配に伴う低線量放射線リスクの上振れ　　　　　　　　　　　　　　　
挑戦的研究（萌芽）
Jul. 2022 - Mar. 2025

高感度検出系を用いた低濃度地リチウム水が誘発する突然変異の線量率依存性の解明　　　　　　　　　　　　　　　
基盤研究（C）
Apr. 2019 - Mar. 2022

水戸市防災会議 委員　　　　　　　　　　　　　　
others
水戸市, 02 Apr. 2018 - Present

原子力と放射線 なんでもQ&A　　　　　　　　　　　　　　
appearance
茨城県原子力安全対策課, 茨城放送, 12 Feb. 2024 - 29 Feb. 2024

「放射線教育コアティーチャー研修」廃炉に向けた課題、トリチウムと放射線生体影響　　　　　　　　　　　　　　
lecturer
科学技術振興財団, 放射線教育コアティーチャー研修会, 26 Dec. 2023

トリチウムの生体影響について：科学的な視点から　　　　　　　　　　　　　　
contribution
NPO法人 食の安全と安心を科学する会, 食の安全と安心通信 Vol.51, 01 Dec. 2023

アインシュタインスクール「放射線・原子力の基礎講座」放射線の基礎と生体影響　　　　　　　　　　　　　　
lecturer
ひたちなか市、および（公社）茨城原子力協議会, 10 Sep. 2023

Opinion: ,Fukushima water release must be judged on scientific evidence: Concentrations of radiation in the Pacific will not rise significantly.
contribution
日本経済新聞社, Nikkei Asia, 28 Jul. 2023

原子力と放射線、なんでもQ&A　　　　　　　　　　　　　　
appearance
茨城県、茨城放送, 茨城放送, Feb. 2023 - Mar. 2023

原子力と放射線、なんでもQ&A　　　　　　　　　　　　　　
appearance
茨城県、茨城放送, 茨城放送, Feb. 2022

日本国際放送のアジア向け番組出演　　　　　　　　　　　　　　
appearance
日本国際放送, Jan. 2022

アインシュタインスクール「原子力と放射線の基礎講座」：放射線の基礎　　　　　　　　　　　　　　
appearance
（公社）茨城原子力協議会, 30 Oct. 2021

アインシュタインスクール「原子力と放射線の基礎講座」第1回　　　　　　　　　　　　　　
appearance
（公社）茨城原子力協議会, 19 Sep. 2020

大人のための科学教室 講師　　　　　　　　　　　　　　
lecturer
日立シビックセンター, 2017 - 2018

サイエンスアゴラ参加企画「私たちは福島原発事故から何を学んだか」　　　　　　　　　　　　　　
panelist
科学技術振興機構, サイエンスアゴラ2017, 26 Nov. 2017 - 26 Nov. 2017

原子力と放射線の基礎知識普及啓発講座 講師　　　　　　　　　　　　　　
lecturer
公益社団法人 茨城原子力協議会, 2015

放射線影響に関する基礎事項解説　　　　　　　　　　　
茨城放送, 原子力と放射線 なんでもQ&A, Feb. 2024, Media report

Fukushima water release must be judged on scientific evidence: Concentrations of radiation in the Pacific will not rise significantly.　　　　　　　　　　　
Nikkei Asia, Jul. 2023, Paper

福島第一原発の処理水に関する論考　　　　　　　　　　　
産経新聞社, 産経新聞, 14 Mar. 2021, Paper

放射線とその健康影響に関する解説　　　　　　　　　　　
茨城放送, 原子力と放射線なんでもQ&A, Feb. 2021, Media report

トリチウムに関する解説　　　　　　　　　　　
福島民友新聞, 14 Feb. 2020, Paper