Ren Wendan, Chen Hongxia, Sun Qiangzu, Tang Xuhua, Lim Siew Choo, Huang Jun, Song Haiwei
Life Sciences Institute, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, China; Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Life Sciences Institute, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, China.
Cell Rep. 2014 Mar 27;6(6):982-991. doi: 10.1016/j.celrep.2014.02.020. Epub 2014 Mar 13.
The SOSS1 complex comprising SOSSA, SOSSB1, and SOSSC senses single-stranded DNA (ssDNA) and promotes repair of DNA double-strand breaks (DSBs). But how SOSS1 is assembled and recognizes ssDNA remains elusive. The crystal structure of the N-terminal half of SOSSA (SOSSAN) in complex with SOSSB1 and SOSSC showed that SOSSAN serves as a scaffold to bind both SOSSB1 and SOSSC for assembly of the SOSS1 complex. The structures of SOSSAN/B1 in complex with a 12 nt ssDNA and SOSSAN/B1/C in complex with a 35 nt ssDNA showed that SOSSB1 interacts with both SOSSAN and ssDNA via two distinct surfaces. Recognition of ssDNA with a length of up to nine nucleotides is mediated solely by SOSSB1, whereas neither SOSSC nor SOSSAN are critical for ssDNA binding. These results reveal the structural basis of SOSS1 assembly and provide a framework for further study of the mechanism governing longer ssDNA recognition by the SOSS1 complex during DSB repair.
由SOSSA、SOSSB1和SOSSC组成的SOSS1复合物可感知单链DNA(ssDNA)并促进DNA双链断裂(DSB)的修复。但SOSS1如何组装并识别ssDNA仍不清楚。SOSSA(SOSSAN)N端一半与SOSSB1和SOSSC形成复合物的晶体结构表明,SOSSAN作为支架结合SOSSB1和SOSSC以组装SOSS1复合物。SOSSAN/B1与12个核苷酸的ssDNA形成复合物以及SOSSAN/B1/C与35个核苷酸的ssDNA形成复合物的结构表明,SOSSB1通过两个不同表面与SOSSAN和ssDNA相互作用。长度达九个核苷酸的ssDNA的识别仅由SOSSB1介导,而SOSSC和SOSSAN对ssDNA结合均不重要。这些结果揭示了SOSS1组装的结构基础,并为进一步研究DSB修复过程中SOSS1复合物识别更长ssDNA的机制提供了框架。