<scp>PRMT4</scp>/<scp>CARM1</scp> Is a Novel Factor Promoting <scp>DNA</scp> Double‐Strand Break Repair

DNA double-strand breaks (DSBs), among the most deleterious forms of DNA damage, are primarily repaired by non-homologous end-joining or homologous recombination repair in mammalian cells. Although DSB repair is regulated by various posttranslational modifications, such as phosphorylation, the contribution of protein arginine methylation, catalyzed by protein arginine N-methyltransferases (PRMTs), is less understood. To explore this, we conducted a screen of human PRMTs for their recruitment to the DSB sites in living cells. Among the hits, PRMT4 (also known as coactivator-associated arginine methyltransferase 1: CARM1) was found to accumulate at the DSB sites within 1 min, with the signal dissipating by 10 min post-damage. Further analysis revealed that PRMT4 recruitment to DSB sites depended on its interaction with PARP1, in which both N- and C-terminal domains of PRMT4 were required. In addition, the catalytic activity of PRMT4 was indispensable for releasing PRMT4 from the DSB sites. Finally, the PRMT4 knockout cell line exhibited delayed DSB repair, as evidenced by the neutral comet assay. Consistently, this cell line displayed a higher residual γH2AX signal compared to the parental cells following phleomycin treatment. Collectively, our findings extend the list of PRMTs involved in maintaining genome integrity and identify PRMT4 as a novel factor promoting DSB repair.