2002 Fiscal Year Final Research Report Summary
Mechanisms of the primary repair for the radiation-induced DNA (damage
| Project/Area Number |
13670976
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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 |
Radiation science
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
KASAI Masataka National Institute of Infectious Diseases, Department of Immunology, 免疫部, 主任研究員 (10142134)
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| Project Period (FY) |
2001 – 2002
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| Keywords | radiation / Translin / DNA-PK / Atm / Mice deficient in Translin / C1D |
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| Research Abstract |
Expression of Translin closely parallels the proliferative state in various cell types. Confocal microscopic analysis revealed that Translin is localized at the centrosomes at prophase and the mitotic spindle at metaphase, then translocating to the spindle midbodies during cytokinesis. The results suggest that Translin participates in processes ensuring the segregation of chromosomes and cytokinesis. Ataxia-telangiectasia (AT) is a recessive human genetic disorder resulting from mutations of Atm gene, characterized by progressive neuro-degeneration, immunologic defects, cancer predisposition, and hypersensitivity to ionizing radiation. AT cells show irradiation-induced cell-cycle checkpoint defects. To address the link between Translin and cell proliferation, we tested the Translin levels in Atm-deficient mice after exposure to ionizing radiation. The results clearly indicate that down-regulation of the Translin levels in spleen cells of wild mice, Atm(+/+), occurred within 24 hrs of irradiation, while those in Atm(-/-) mice did not change at all, consistent with the lack of cell-cycle arrest. Mice deficient in Translin are significantly smaller than control littermates and the lymphocyte development is arrested at the earliest progenitor stages. Since the nuclear matrix protein C1D, an activator of the DNA dependent protein kinase (DNA-PK), is known to affect the function of Translin, we are studying the repair mechanisms for the radiation-induced DNA damage in the mutant mice.
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[Publications] Sugiura, I, Sasaki, C, Hasegawa, T, Kohno, Sugio, T, Moriyama, H, Kasai, M and Matsuzaki, T: "Crystal structure of human Translin at 2.2A resolution"Acta Cryst. D. In press. (2003)
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[Publications] Ishida, R., Okado, H., Sato, H., Shionoiri, C. Aoki, K., and Kasai M.: "A role for the octameric ring protein, Translin, in mitotic cell division"FEBS Lett.. 525. 105 (2002)
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[Publications] Hosaka, T., Kanoe, H., Nakayama, T., Murakami, H., Yamamoto, H., Nakamata, T., Tsuboyama, T., Oka, M., Kasai, M., Sasaki, M., Nakamura, T., and Toguchida J.: "Trarislin binds to the sequences adjacent to the breakpoints of the TLS and CHOP genes in liposarcomas with translocation t(12;6)"Oncogene. 19. 5821-5825 (2000)
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[Publications] Meng, G., Inazawa, J., Ishida, R., Tokura, K., Nakahara, K., Aoki, K., and Kasai, M.: "Genomic structure and chromosomal localization of the gene encoding TRAX, a Translin-associated factor X"J. Hum. Genet. 45. 305-308 (2000)
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