Hwang, Jee Won Kim, Su-Nam Myung, Nayeon Song, Doona Han, Gyoonhee Bae, Gyu-Un Bedford, Mark T. Kim, Yong Kee 2024-01-19T17:02:21Z 2024-01-19T17:02:21Z 2021-09-02 2020-08 2399-3642 https://pubs.kist.re.kr/handle/201004/118334 Hwang et al. show that the activity of PRMT5 methyltransferase is regulated by Src kinase-mediated phosphorylation at Y324 in response to DNA damage. They also show that PRMT5 participates in NHEJ repair by regulating 53BP1 protein levels and is critical for cellular survival after DNA damage. PRMT5 participates in various cellular processes, including transcription regulation, signal transduction, mRNA splicing, and DNA repair; however, its mechanism of regulation is poorly understood. Here, we demonstrate that PRMT5 is phosphorylated at residue Y324 by Src kinase, a negative regulator of its activity. Either phosphorylation or substitution of the Y324 residue suppresses PRMT5 activity by preventing its binding with the methyl donor S-adenosyl-L-methionine. Additionally, we show that PRMT5 activity is associated with non-homologous end joining (NHEJ) repair by methylating and stabilizing p53-binding protein 1 (53BP1), which promotes cellular survival after DNA damage. Src-mediated phosphorylation of PRMT5 and the subsequent inhibition of its activity during the DNA damage process blocks NHEJ repair, leading to apoptotic cell death. Altogether, our findings suggest that PRMT5 regulates DNA repair through Src-mediated Y324 phosphorylation in response to DNA damage. English Nature Publishing Group PRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation Article 10.1038/s42003-020-01157-z 1 Communications Biology, v.3, no.1 Communications Biology 3 1 Y scie scopus 000562860000003 2-s2.0-85088997357 Biology Multidisciplinary Sciences Life Sciences & Biomedicine - Other Topics Science & Technology - Other Topics Article DOUBLE-STRAND BREAKS ARGININE METHYLATION TRANSCRIPTIONAL REPRESSION PROTEIN METHYLTRANSFERASE DIMETHYLATION EXPRESSION STABILITY DEFECTS CELLS