Arginine methylation and ubiquitylation crosstalk controls DNA end resection and homologous recombination repair
María Pilar Sánchez-Bailón
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch [Berlin, Germany]
Arginine methylation is a post-translational modification catalyzed by Protein arginine methyltransferases (PRMTs). The PRMT family is composed of nine members with essential functions for the cell including transcription, splicing, signal transduction, cell cycle and DNA damage repair. There are two main PRMTs, PRMT5 and PRMT1, the last one is an asymmetric dimethyltransferase responsible for 85% of all cellular arginine methylation. We have identified the deubiquitylating enzyme USP11 as a previously uncharacterised PRMT1 substrate, and showed that the methylation of USP11 promotes DNA end-resection and the repair of DNA double strand breaks by homologous recombination (HR). We also have observed that PRMT1 is a ubiquitylated protein that it is targeted for deubiquitylation by USP11, which regulates the ability of PRMT1 to bind to and methylate MRE11, a key player in double strand breaks repair.