RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1.
RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1.
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DOI：
10.1093/nar/gkp082
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发表时间：
2009-04
影响因子：
14.9
通讯作者：
Tateishi S
中科院分区：
文献类型：
--
作者：
Watanabe K;Iwabuchi K;Sun J;Tsuji Y;Tani T;Tokunaga K;Date T;Hashimoto M;Yamaizumi M;Tateishi S
招募的RAD 18停滞的复制叉促进monoubiquitination的PCNA在S期，促进translesion合成在网站的紫外线照射诱导的DNA损伤。在这项研究中，我们发现RAD 18也被募集到电离辐射（IR）诱导的DNA双链断裂（DSB）位点，形成与53 BP 1，NBS 1，磷酸化ATM，BRCA 1和γ-H2 AX共定位的病灶。RAD 18与53 BP 1结合并以53 BP 1依赖的方式被募集到DSB位点，特别是在G1期，RAD 18在体外在赖氨酸1268处单泛素化53 BP 1的KBD结构域。在赖氨酸1268处具有取代的单泛素化抗性53 BP 1突变体不能有效地保留在DSB附近的染色质上。在Rad 18-null细胞中，与野生型细胞相比，53 BP 1病灶的保留、DSB修复效率和照射后活力受损。综上所述，这些结果表明，RAD 18通过增强53 BP 1的保留，可能通过RAD 18和53 BP 1之间的相互作用和53 BP 1的修饰，促进53 BP 1指导的DSB修复。
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. A monoubiquitination-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.
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影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
16
作者：
Lou, ZK;Minter-Dykhouse, K;Chen, JJ
通讯作者：
Chen, JJ
DOI：
10.1073/pnas.0830918100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Rothkamm, K;Löbrich, M
通讯作者：
Löbrich, M
影响因子：
9.2
作者：
Paull, TT;Rogakou, EP;Bonner, WM
通讯作者：
Bonner, WM
影响因子：
16
作者：
Kannouche, PL;Wing, J;Lehmann, AR
通讯作者：
Lehmann, AR