hSWS1.SWSAP1 Is an Evolutionarily Conserved Complex Required for Efficient Homologous Recombination Repair
hSWS1.SWSAP1 Is an Evolutionarily Conserved Complex Required for Efficient Homologous Recombination Repair
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DOI：
10.1074/jbc.m111.271080
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发表时间：
2011-12-02
影响因子：
4.8
通讯作者：
Huang, Jun
中科院分区：
文献类型：
--
作者：
Liu, Ting;Wan, Li;Huang, Jun
酵母中的Shu复合物在同源重组途径中起着重要作用，对于维持基因组的完整性至关重要。人SWS 1（hSWS 1）作为芽殖酵母Shu 2的同源物的鉴定暗示Shu复合物在进化上是保守的。然而，在这个复杂的其他组件的人类对应物尚未被确定和表征。在这里，我们描述了一个新的人类组成部分，这种复杂的，SWSAP 1（hSWS 1相关蛋白1）/C19 orf 39的表征。我们发现，hSWS 1和SWSAP 1在体内和体外形成稳定的复合物。hSWS 1和SWSAP 1的稳定性相互依赖。我们进一步证明了纯化的hSWS1.SWSAP1复合物具有单链DNA结合活性和DNA刺激的ATP酶活性。此外，SWSAP 1与RAD 51和RAD 51旁系同源物相互作用，SWSAP 1的缺失导致同源重组修复缺陷。因此，我们的研究结果表明，人类Shu复合物（hSWS1.SWSAP1）在同源重组中具有进化上保守的功能。
The Shu complex in yeast plays an important role in the homologous recombination pathway, which is critical for the maintenance of genomic integrity. The identification of human SWS1 (hSWS1) as the homolog of budding yeast Shu2 implicated that the Shu complex is evolutionarily conserved. However, the human counterparts of other components in this complex have not yet been identified and characterized. Here we describe the characterization of a novel human component of this complex, SWSAP1 (hSWS1-associated protein 1)/C19orf39. We show that hSWS1 and SWSAP1 form a stable complex in vivo and in vitro. hSWS1 and SWSAP1 are mutually interdependent for their stability. We further demonstrate that the purified hSWS1.SWSAP1 complex possesses single-stranded DNA-binding activity and DNA-stimulated ATPase activity. Moreover, SWSAP1 interacts with RAD51 and RAD51 paralogs, and depletion of SWSAP1 causes defects in homologous recombination repair. Thus, our results suggest that the human Shu complex (hSWS1.SWSAP1) has an evolutionarily conserved function in homologous recombination.