Structural Basis of SOSS1 Complex Assembly and Recognition of ssDNA

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 (SOSSA(N)) in complex with SOSSB1 and SOSSC showed that SOSSA(N) serves as a scaffold to bind both SOSSB1 and SOSSC for assembly of the SOSS1 complex. The structures of SOSSA(N)/B1 in complex with a 12 nt ssDNA and SOSSA(N)/B1/C in complex with a 35 nt ssDNA showed that SOSSB1 interacts with both SOSSA(N) 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 SOSSA(N) 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.