2003 Fiscal Year Final Research Report Summary
Maintenance of genomic stability by postreplication repair
| Project/Area Number |
14572144
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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 |
Human genetics
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| Research Institution | Kumamoto University |
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Principal Investigator |
TATEISHI Satoshi Kumamoto University, Inst.Mol.Embryol. & Genet., Lecturer, 発生医学研究センター, 講師 (00227109)
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| Project Period (FY) |
2002 – 2003
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| Keywords | RAD18 / postreplication repair / translesion synthesis / ubiquitin / PCNA / polymerase |
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| Research Abstract |
DNA polymerase often stalls at damaged sites on templates, however usually restarts by switching to special DNA polymerases that carry out translesion synthesis (TLS). DNA damaged sites, which is a crucial step for UV-induced TLS. We establish RAD18-/-cell lines and show that pol eta accumulates at replication foci in Rad18 depended manner, resulting in co-localization foci, suggesting that Rad18 recruit pol eta to the site. PCNA is mono-ubiquitinated in Rad18 and hHR6-dependent manner. In vitro, purified Rad18 and Rad6 mono-ubiquitinates PCNA. In our model, Rad18 is a crucial molecule for recruitment and replacement of DNA polymerase eta. We established Rad18-KO mice and observed those pherotypes including sensitivity to radiation.
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Research Products
(11 results)
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[Publications] Yamashita, Y.M., Okada, T., Matsusaka, T., Sonoda, E., Zhao, G.Y., Araki, K., Tateishi, S., Yamaizumi M., Takeda S.: "RAD18 and RAD54 cooperatively contribute to maintenance of genomic stability in vertebrate cells."The EMBO Journal. 21(20). 5558-5566 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Okada, T., Sonoda, E., Yamashita, Y.M., Koyoshi, S., Tateishi, S., Yamaizumi, M., Takata, M., Ogawa, O., Takeda, S.: "Involvement of Vertebrate Pol k in Rad18-independent Postreplication Repair of UV damage."J.Biol.Chem.. 227(50). 48690-48695 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Tateishi, S., Niwa, H., Miyazaki, J., Fujimoto, S., Inoue, H., Yamaizumi, M.: "Enhanced Genomic Instability and Defective Postreplication Repair in RAD18 Knockout Mouse Embryonic Stem Cells."Mol.Cell.Biol.. 23(2). 474-481 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Sonoda, E., Okada, T., Zhao, G.Y., Tateishi, S., Araki, K., Yamaizumi, M., Yagi, T., Verkaik, N.M., van Gents, D.C., Takata M., Takeda S.: "Multiple roles of Rev3, the catalytic subunit of polz in maintaining genome stability in vertebrate."The EMBO Journal. 22(12). 3188-3197 (2003)
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「研究成果報告書概要(欧文)」より
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