RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1
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- TATEISHI Satoshi
- Kumamoto Univ. IMEG
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- IWABUCHI Kuniyoshi
- Kanazawa Medical University School of Medicine
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- WATANABE Kenji
- Denmark, Institute of Cancer Biology
Bibliographic Information
- Other Title
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- Rad18は、53BP1をモノユビキチン化することにより、G1期でのDNA2重鎖切断損傷の修復を促進する。
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Abstract
Recruitment of RAD18 to stalled replication forks facilitates monoubiquitination of PCNA during S-phase, promoting translesion synthesis at sites of UV irradiation-induced DNA damage. In this study, we show that RAD18 is also recruited to ionizing radiation (IR)-induced sites of DNA double-strand breaks (DSBs) forming foci which are co-localized with 53BP1, NBS1, phosphorylated ATM, BRCA1, and γ-H2AX. RAD18 associates with 53BP1 and is recruited to DSB sites in a 53BP1-dependent manner specifically during G1-phase, RAD18 monoubiquitinates KBD domain of 53BP1 at lysine 1268 in vitro. 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, efficiency of DSB repair, and post-irradiation viability are impaired compared with wild-type cells. Taken together, these results suggest that RAD18 promotes 53BP1-directed DSB repair by enhancing retention of 53BP1, possibly through an interaction between RAD18 and 53BP1 and the modification of 53BP1.
Journal
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- The Japan Radiation Research Society Annual Meeting Abstracts
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The Japan Radiation Research Society Annual Meeting Abstracts 2009 (0), 81-81, 2009
The Japanese Radiation Research Society
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Details 詳細情報について
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- CRID
- 1390001205642515584
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- NII Article ID
- 130005443392
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- Data Source
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- JaLC
- CiNii Articles
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- Abstract License Flag
- Disallowed