Characterizing a role of RBM15B in  DNA Repair

DNA double-strand breaks (DSBs) are considered among the most cytotoxic DNA lesions. Cells utilize various DSB repair pathways, including homologous recombination (HR), which is executed at S/G2 phases of the cell cycle. Interestingly, RNA modifications and RNA-binding proteins have essential roles in HR repair. The RNA-Binding Motif 15B (RBM15B) protein is implicated in m6A positioning on RNA, but its role in DNA damage remains elusive. Here, we show that RBM15B is rapidly recruited to DSB sites. Moreover, we show that RBM15B negatively regulates R-loop and global N6-methyladenosine (m6A) levels on RNA, consequently promoting HR repair of DSBs. Accordingly, RBM15B-deficient cells show an increase in the levels of the replication stress markers pCHK1(S345) and pRPA32(S33), and are hypersensitive to various genotoxic agents. Collectively, our data establish RBM15B as a novel regulator of HR repair of DSBs, presumably by regulating the cellular levels of m6A and R-loops