Regulation of DNA repair through deSUMOylation and SUMOylation of replication protein A complex.
Regulation of DNA repair through deSUMOylation and SUMOylation of replication protein A complex.
复制标题
DOI：
10.1016/j.molcel.2010.07.021
复制
发表时间：
2010-08-13
期刊：
影响因子：
16
通讯作者：
Yeh ET
中科院分区：
文献类型：
--
作者：
Dou H;Huang C;Singh M;Carpenter PB;Yeh ET
复制蛋白A复合体（RPA）在DNA复制和损伤反应中起着至关重要的作用。然而，尚不清楚该复合物是否受SUMOylation途径的调节。在这里，我们发现RPA的70kd亚基（RPA70）与细胞核中的Sentrin/ sumo特异性蛋白酶SENP6结合，以维持RPA70在S期处于低sumo化状态。Campothecin （CPT）是一种复制胁迫诱导剂，可以将SENP6与RPA70分离，从而使RPA70被一个小的泛素样修饰物2/3 （SUMO-2/3）修饰。RPA70 summoylation促进Rad51募集到DNA损伤灶，通过同源重组（homologous recombination， HR）启动DNA修复。表达不能被SUMOylated的RPA70突变的细胞系在HR中存在缺陷，并且对CPT的敏感性显着增加。这些结果表明，RPA70的SUMOylation状态在通过同源重组调控DNA修复中起着关键作用。
The replication protein A complex (RPA) plays a crucial role in DNA replication and damage response. However, it is not known whether this complex is regulated by the SUMOylation pathway. Here we show that the 70kd subunit of RPA (RPA70) associates with a Sentrin/SUMO-specific protease, SENP6, in the nucleus to maintain RPA70 in a hypo-SUMOylated state during S phase. Campothecin (CPT), an inducer of replication stress, dissociates SENP6 from RPA70 allowing RPA70 to be modified by a small ubiquitin-like modifier 2/3 (SUMO-2/3). RPA70 SUMOylation facilitates recruitment of Rad51 to the DNA damage foci to initiate DNA repair through homologous recombination (HR). Cell lines that expressed a RPA70 mutant that cannot be SUMOylated are defective in HR and have a marked increase in sensitivity to CPT. These results demonstrate that SUMOylation status of RPA70 plays a critical role in the regulation of DNA repair through homologous recombination.
登录
查看更多内容
影响因子：
3.8
作者：
Heideker, J.;Perry, J. J. P.;Boddy, M. N.
通讯作者：
Boddy, M. N.
影响因子：
21.3
作者：
Kittler, Ralf;Pelletier, Laurence;Buchholz, Frank
通讯作者：
Buchholz, Frank
DOI：
10.1073/pnas.131009198
发表时间：
2001-07-17
影响因子：
11.1
作者：
Kuzminov, A
通讯作者：
Kuzminov, A
影响因子：
3.7
作者：
Häkli, M;Karvonen, U;Palvimo, JJ
通讯作者：
Palvimo, JJ
DOI：
10.1073/pnas.211322798
发表时间：
2001-10-09
影响因子：
11.1
作者：
Gilbert, N;Allan, J
通讯作者：
Allan, J