Switch-like phosphorylation of WRN integrates end-resection with RAD51 metabolism at collapsed replication forks.

ABSTRACT: Replication-dependent DNA double-strand breaks are harmful lesions preferentially repaired by homologous recombination (HR), a process that requires processing of DNA ends to allow RAD51-mediated strand invasion. End resection and subsequent repair are two intertwined processes, but the mechanism underlying their execution is still poorly appreciated. The WRN helicase is one of the crucial factors for end resection and is instrumental in selecting the proper repair pathway. Here, we reveal that ordered phosphorylation of WRN by the CDK1, ATM and ATR kinases defines a complex regulatory layer essential for correct long-range end resection, connecting it to repair by HR. We establish that long-range end resection requires an ATM-dependent phosphorylation of WRN at Ser1058 and that phosphoryl

SUBMITTER: Palermo V 

PROVIDER: S-EPMC11551760 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature