Cohesin phosphorylation accelerates DNA damage repair and reduces translocations
we describe and clarify several mechanisms whereby ?Cohesin contributes to DNA repair. Upon acute Cohesin depletion, we observed delayed DNA repair and increased frequency of translocations. These translocations were directly correlated to contact frequency between damaged domains. We found that phosphorylation of the Cohesin subunit SMC1A is required to direct specific Cohesin recruitment at DSBs, without affecting its distribution in the undamaged genome. Moreover, Cohesin depletion caused a significant increase in translocations in the 53BP1 deficient background, indicating that Cohesin functions to suppresses 53BP1 independent end joining mechanisms. Our work sheds light on a previously unappreciated mechanisms whereby gCohesin is loaded at DSBs and actively extrudes loops between the break and nearest natural TAD boundary. This process modulates the 3D proximity of broken ends to accelerate repair speeds and prevent long range end joining events during NHEJ. Overall design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for Rad21, Nipbl and Mre11 in HCT116 cells in different genotypic background w/wo DSB and HiC analysis w/wo auxin in DSB.