Huang Jun, Gong Zihua, Ghosal Gargi, Chen Junjie
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Mol Cell. 2009 Aug 14;35(3):384-93. doi: 10.1016/j.molcel.2009.06.011.
Proteins that bind to single-stranded DNA (ssDNA) are essential for DNA replication, recombinational repair, and maintenance of genomic stability. Here, we describe the characterization of an ssDNA-binding heterotrimeric complex, SOSS (sensor of ssDNA) in human, which consists of human SSB homologs hSSB1/2 (SOSS-B1/2) and INTS3 (SOSS-A) and a previously uncharacterized protein C9orf80 (SOSS-C). We have shown that SOSS-A serves as a central adaptor required not only for SOSS complex assembly and stability, but also for facilitating the accumulation of SOSS complex to DNA ends. Moreover, SOSS-depleted cells display increased ionizing radiation sensitivity, defective G2/M checkpoint, and impaired homologous recombination repair. Thus, our study defines a pathway involving the sensing of ssDNA by SOSS complex and suggests that this SOSS complex is likely involved in the maintenance of genome stability.
与单链DNA(ssDNA)结合的蛋白质对于DNA复制、重组修复以及基因组稳定性的维持至关重要。在此,我们描述了一种人类中的ssDNA结合异源三聚体复合物SOSS(单链DNA传感器)的特性,它由人类SSB同源物hSSB1/2(SOSS-B1/2)和INTS3(SOSS-A)以及一种此前未被表征的蛋白质C9orf80(SOSS-C)组成。我们已经表明,SOSS-A不仅是SOSS复合物组装和稳定性所需的核心衔接蛋白,而且还促进SOSS复合物在DNA末端的积累。此外,SOSS缺失的细胞表现出电离辐射敏感性增加、G2/M检查点缺陷以及同源重组修复受损。因此,我们的研究定义了一条涉及SOSS复合物感知ssDNA的途径,并表明该SOSS复合物可能参与基因组稳定性的维持。