| Project/Area Number |
20510056
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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 |
Risk sciences of radiation/Chemicals
|
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
IWABUCHI Kuniyoshi Kanazawa Medical University, 医学部, 教授 (10232696)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Mitsumasa 金沢医科大学, 医学部, 助教 (70293975)
WATANABE Kenji 熊本大学, 発生医学研究センター, 助教 (80404333)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 分子生物学 / 核 / DNA二重鎖切断 / 放射線 / 修復 / ユビキチン / 53BP1 / Rad18 |
|---|
| Research Abstract |
We show that RAD18 is recruited at sites of DNA double-strand breaks (DSBs) forming foci which are co-localized with 53BP1. RAD18 associates with 53BP1 and is recruited at DSB sites in a 53BP1-dependent manner specifically during G1-phase. RAD18 mono- ubiquitinates 53BP1 at lysine 1268 in vitro. The mono-ubiquitination resistant 53BP1 mutant harboring a substitution at lysine 1268 is not retained efficiently at the chromatin in the vicinity of DSBs. In Rad18-null cells, retention of 53BP1 foci, efficacy of DSB repair and post-irradiation viability are impaired compared with wild-type cells. Taken together, these results suggest that RAD18 promotes 53BP1- mediated DSB repair by enhancing retention of 53BP1, possibly through an interaction between RAD18 and 53BP1 and the mono-ubiquitination of 53BP1.
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