. PRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation.
- . PRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation.
- 김수남; 황지원; 명나연; 송두나; 한균희; 배규운; Mark T. Bedford; 김용기
- Issue Date
- Communications biology
- VOL 3, NO 1, 428
- 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 Sadenosyl-L-methionine. Additionally, we show that PRMT5 activity is associated with nonhomologous 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.
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