A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination
A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination
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DOI：
10.1016/j.molcel.2007.01.029
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发表时间：
2007-03-09
期刊：
影响因子：
16
通讯作者：
Takeda, Shunichi
中科院分区：
文献类型：
--
作者：
Zhao, Guang Yu;Sonoda, Eiichiro;Takeda, Shunichi
泛素结合酶Ubc 13参与芽殖酵母中的Rad 6/Rad 18依赖性复制后修复（PRR），但其在脊椎动物中的功能尚不清楚。我们在这里表明，在鸡DT 40或人类细胞中的UBC 13的中断或siRNA耗尽由于染色体不稳定性和对UV和电离辐射的超敏性而赋予严重的生长缺陷，这与UBC 13在PRR中的保守作用一致。值得注意的是，Ubc 13缺陷细胞也会因同源重组（HR）而损害DNA双链断裂（DSB）修复。在Ubc 13缺陷细胞中，BRCA 1的E3 Ub连接酶功能的募集和激活以及随后在DSB处Rad 51核蛋白丝的形成被废除。此外，ssDNA/RPA复合物在DSBs的产生在Ubc 13的情况下严重减弱。这些数据揭示了脊椎动物Ubc 13在DSB处理水平上启动HR中的关键和意想不到的作用。
The ubiquitin (Ub)-conjugating enzyme Ubc13 is implicated in Rad6/Rad18-dependent post-replication repair (PRR) in budding yeast, but its function in vertebrates is not known. We show here that disruption or siRNA depletion of UBC13 in chicken DT40 or human cells confers severe growth defects due to chromosome instability, and hypersensitivity to both UV and ionizing radiation, consistent with a conserved role for Ubc13 in PRR. Remarkably, Ubc13-deficient cells are also compromised for DNA double-strand break (DSB) repair by homologous recombination (HR). Recruitment and activation of the E3 Ub ligase function of BRCA1 and the subsequent formation of the Rad51 nucleoprotein filament at DSBs are abolished in Ubc13-deficient cells. Furthermore, generation of ssDNA/RPA complexes at DSBs is severely attenuated in the absence of Ubc13. These data reveal a critical and unexpected role for vertebrate Ubc13 in the initiation of HR at the level of DSB processing.