GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination.
GEMIN2 promotes accumulation of RAD51 at double-strand breaks in homologous recombination.
复制标题
DOI：
10.1093/nar/gkq271
复制
发表时间：
2010-08
影响因子：
14.9
通讯作者：
Takeda S
中科院分区：
文献类型：
--
作者：
Takizawa Y;Qing Y;Takaku M;Ishida T;Morozumi Y;Tsujita T;Kogame T;Hirota K;Takahashi M;Shibata T;Kurumizaka H;Takeda S
RAD51是同源重组（homologous recombination， HR）中的关键因子，在细胞增殖过程中通过修复DNA复制过程中的损伤发挥重要作用。RAD51在DNA损伤处的组装受到RAD51介质的严格控制，包括BRCA1和BRCA2。我们发现人类RAD51直接结合了参与剪接体生物发生的蛋白GEMIN2/SIP1。生化分析表明，GEMIN2通过抑制RAD51与DNA的解离，促进RAD51- DNA复合物的形成，从而刺激RAD51介导的同源配对。当RPA在加入RAD51之前预结合到ssDNA上时，GEMIN2也增强了RAD51介导的链交换。为了分析GEMIN2的功能，我们在鸡DT40系和人细胞中缺失了GEMIN2。在缺乏BRCA1和BRCA2的细胞中观察到，GEMIN2的缺失降低了HR效率，导致RAD51亚核病灶数量显著减少。这些观察结果和我们的生化分析表明，GEMIN2作为一种新的RAD51介质调节HR。
RAD51 is a key factor in homologous recombination (HR) and plays an essential role in cellular proliferation by repairing DNA damage during replication. The assembly of RAD51 at DNA damage is strictly controlled by RAD51 mediators, including BRCA1 and BRCA2. We found that human RAD51 directly binds GEMIN2/SIP1, a protein involved in spliceosome biogenesis. Biochemical analyses indicated that GEMIN2 enhances the RAD51–DNA complex formation by inhibiting RAD51 dissociation from DNA, and thereby stimulates RAD51-mediated homologous pairing. GEMIN2 also enhanced the RAD51-mediated strand exchange, when RPA was pre-bound to ssDNA before the addition of RAD51. To analyze the function of GEMIN2, we depleted GEMIN2 in the chicken DT40 line and in human cells. The loss of GEMIN2 reduced HR efficiency and resulted in a significant decrease in the number of RAD51 subnuclear foci, as observed in cells deficient in BRCA1 and BRCA2. These observations and our biochemical analyses reveal that GEMIN2 regulates HR as a novel RAD51 mediator.
登录
查看更多内容
影响因子：
5.6
作者：
Aihara, H;Ito, Y;Shibata, T
通讯作者：
Shibata, T
影响因子：
16.8
作者：
Conway, AB;Lynch, TW;Rice, PA
通讯作者：
Rice, PA
影响因子：
4.8
作者：
Fukushima, T;Takata, M;Takeda, S
通讯作者：
Takeda, S
影响因子：
14.9
作者：
Morozumi, Yuichi;Takizawa, Yoshimasa;Kurumizaka, Hitoshi
通讯作者：
Kurumizaka, Hitoshi
影响因子：
16
作者：
Davies, AA;Masson, JY;West, SC
通讯作者：
West, SC