Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Department of Experimental Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030.
J Biol Chem. 2011 Dec 2;286(48):41758-41766. doi: 10.1074/jbc.M111.271080. Epub 2011 Sep 29.
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.
酵母中的 Shu 复合物在同源重组途径中发挥着重要作用，该途径对于维持基因组完整性至关重要。芽殖酵母 Shu2 的同源物人 SWS1（hSWS1）的鉴定表明，Shu 复合物在进化上是保守的。然而，该复合物的其他成分的人类对应物尚未被鉴定和表征。在这里，我们描述了该复合物的一个新的人类成分，SWSAP1（hSWS1 相关蛋白 1）/C19orf39 的特征。我们表明 hSWS1 和 SWSAP1 在体内和体外形成稳定的复合物。hSWS1 和 SWSAP1 相互依赖以维持其稳定性。我们进一步证明，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，SWSAP1 与 RAD51 和 RAD51 同源物相互作用，SWSAP1 的耗竭导致同源重组修复缺陷。因此，我们的结果表明，人类 Shu 复合物（hSWS1·SWSAP1）在同源重组中具有进化上保守的功能。
