Molecular mechanisms of induction and suppression of mutations accompanied with bypass of DNA damages
| Project/Area Number |
17013041
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
OHMORI Haruo Kyoto University, ウイルス研究所, 准教授 (10127061)
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| Project Period (FY) |
2005 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥48,500,000 (Direct Cost: ¥48,500,000)
Fiscal Year 2009: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2008: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2007: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2006: ¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 2005: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | DNA損傷バイパス / YファミリーDNAポリメラーゼ / 突然変異誘発 / 分子間相互作用 / 結合認識配列 / 細胞周期チェックポイント / 結合モチーフ配列 / REV3 / REV7 / MAD2 / DAN損傷バイパス / DNAポリメラーゼ / PCNA / Polκ / Polη / Polζ / DNA損傷 / 損傷バイパス合成 / タンパク間相互作用 / MAD2L2 / 損傷バイパス / 突然変異 / 発がん / ベンゾピレン / 皮膚ガン / 肺がん / 免疫遺伝子 / 体細胞超変異 / ピエシリン |
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| Research Abstract |
Mammalians have multiple DNA polymerases for translesion DNA synthesis (TLS), which show different specificities for lesions to bypass. In order to investigate how a TLS DNA polymerase appropriate for bypassing a given DNA lesion is recruited, we studied on the interactions of human Polκ, Polη or Polι with other proteins. Polκ, Polη and Polι each interact with a C-terminal region of REV1 (REV1-CTD). We found 1) interaction of Polk with REV1-CTD is necessary for its functions, 2) the interaction of Polη is not required for the enzyme to bypass UV-induced lesions, but it may be required for the enzyme to bypass other lesions. Polη interacts with PCNA and also with Rad6-Rad18 complex that ubiquitinates PCNA in DNA-damaged cells. Therefore, Polη likely has a priority to bind Ub-PCNA when Rad6-Rad18 complex modifies PCNA in a stalled replication fork. When Polη cannot bypass the lesion in the stalled replication fork, switching from Polη to another TLS DNA polymerase may occur through their interactions with REV1-CTD.
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Report
(6 results)
Research Products
(33 results)
