2001 Fiscal Year Final Research Report Summary
Role of NBS1 in Repair of DNA damage Induced by Ionizing Radiation
| Project/Area Number |
12680543
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | IBARAKI UNIVERSITY (2001)
Hiroshima University (2000) |
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Principal Investigator |
TAUCHI Hiroshi IBARAKI Univ., Faculty of Science, Associate professor, 理学部, 助教授 (70216597)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Shinya HIROSHIMA Univ., Dept. Rad. Biol., Assoclate Professor, 原爆放射能医学研究所, 助教授 (90274133)
KOMATSU Kenshi HIROSHIMA Univ., Dept. Rad. Biol., Professor, 原爆放射能医学研究所, 教授 (80124577)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Radiation sensitivity / DNA repair / Homologous recombination / Gene knockout |
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| Research Abstract |
NBS1 (p95) is the protein responsible for Nijmegen breakage syndrome (NBS), a variant of ataxia-telangiectasia. Disruption of NBS1 in NBS patients leads to hyper-sensitivity to ionizing radiation, chromosomal instability, and a predisposition to cancer. NBS1 is a homologue of yeast (Saccharomyces celevisiae) Xrs2 protein which is known to interact with Mre11/Rad50 to form a complex with a nuclease and DNA annealing activity. In yeast, the complex activity is essential for initiation of homologous DNA recombination (HR) at meiosis whereas it is also involved in recombination of DNA double-strand breaks (DSB) in mitotic cells.
To investigate the function of Nbs1 on DNA repair in higher vertebrate cells, we constructed a Nbs1-knockout cell line using chicken B-lymphocyte DT40. Although DT40 has three Nbs1 alleles, those alleles were successfully targeted. The Nbs1-/-/- cells were viable although they showed. The Nbs1-/-/- cells showed apparent increase of chromatid breaks and gaps after irradiation, hyper-sensitivity to radiation, and radiation-resistant DNA synthesis which is known as a deficiency of S-phase checkpoint. These phenotypes were similar to those of NBS patient cells, suggesting that NBS1 is essential for DNA repair or cell cycle checkpoints responding to DNA damage induced by ionizing radiation.
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[Publications] Hama, S., Matsuura, S., Tauchi, H., Sawada, J., Kato, C., Yamasaki, F., Yoshioka, H., Sugiyama, K., Arita, K., Kurisu, K., Kamada, N., Heike, Y., Komatsu, K.: "Absence of mutation in the NBS1 gene in B-cell malignant lymphoma patients"Anticancer Ressearch. 20. 1897-1900 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Tauchi, H., Kobayashi, J., Morishima, K., Matsuura, S., Nakamura, A., Shiraishi, T., Ito, E., Masnada, D., Delia, D., Komatsu, K.: "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"Journal of Biological Chemistry. 276. 12-15 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Buscemi G, Savio C, Zannini L, Micciche F, Masnada D, Nakanishi M, Tauchi H,- Komatsu K, Mizutani S, Khanna K, Chen P, Concannon P, Chessa L, Delia D.: "Chk2 activation dependence on Nbs1 after DNA damage"Molecular and Cellular Biology. 21. 5124-5222 (2001)
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「研究成果報告書概要(欧文)」より
