Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks
Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks
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DOI：
10.1038/sj.emboj.7601218
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发表时间：
2006-07-26
期刊：
影响因子：
11.4
通讯作者：
Yu, Hongtao
中科院分区：
文献类型：
--
作者：
Potts, Patrick Ryan;Porteus, Matthew H.;Yu, Hongtao
染色体结构维持蛋白（SMC）家族参与同源重组（HR）修复DNA双链断裂（DSB）。SMC 1/3粘附素复合物被认为通过维持姐妹染色单体在DSB处的紧密接近来促进HR。SMC 5/6复合物也是DNA修复所必需的，但其实现这一点的机制尚不清楚。在这里，我们表明，由于姐妹染色单体HR中对hSMC 5/6的特定需求，RNAi介导的人细胞中SMC 5/6复合物组分的敲低增加了基因靶向的效率。hSMC 5/6复合物的敲低降低了姐妹染色单体HR，但不降低非同源末端连接（NHEJ）或染色单体内同源物，hSMC 5/6复合物本身被募集到核酸酶诱导的DSB中，并且是将粘着蛋白募集到DSB中所需的。我们的研究结果建立了一种机制，hSMC 5/6复合物促进DNA修复，并提出了一种新的策略，以提高效率的基因打靶在哺乳动物体细胞。
The structural maintenance of chromosomes (SMC) family of proteins has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The SMC1/3 cohesin complex is thought to promote HR by maintaining the close proximity of sister chromatids at DSBs. The SMC5/6 complex is also required for DNA repair, but the mechanism by which it accomplishes this is unclear. Here, we show that RNAi-mediated knockdown of the SMC5/6 complex components in human cells increases the efficiency of gene targeting due to a specific requirement for hSMC5/6 in sister chromatid HR. Knockdown of the hSMC5/6 complex decreases sister chromatid HR, but does not reduce nonhomologous endjoining (NHEJ) or intra-chromatid, homologue, or extrachromosomal HR. The hSMC5/6 complex is itself recruited to nuclease-induced DSBs and is required for the recruitment of cohesin to DSBs. Our results establish a mechanism by which the hSMC5/6 complex promotes DNA repair and suggest a novel strategy to improve the efficiency of gene targeting in mammalian somatic cells.