PRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation.
Commun Biol
; 3(1): 428, 2020 08 05.
Article
em En
| MEDLINE
| ID: mdl-32759981
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.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
Base de dados:
MEDLINE
Assunto principal:
Proteína-Arginina N-Metiltransferases
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Quinases da Família src
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Proteína 1 de Ligação à Proteína Supressora de Tumor p53
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Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2020
Tipo de documento:
Article