Phosphoregulation of DNA repair via the Rad51 auxiliary factor Swi5-Sfr1.
J Biol Chem
; 299(8): 104929, 2023 08.
Article
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| MEDLINE
| ID: mdl-37330173
ABSTRACT
Homologous recombination (HR) is a major pathway for the repair of DNA double-strand breaks, the most severe form of DNA damage. The Rad51 protein is central to HR, but multiple auxiliary factors regulate its activity. The heterodimeric Swi5-Sfr1 complex is one such factor. It was previously shown that two sites within the intrinsically disordered domain of Sfr1 are critical for the interaction with Rad51. Here, we show that phosphorylation of five residues within this domain regulates the interaction of Swi5-Sfr1 with Rad51. Biochemical reconstitutions demonstrated that a phosphomimetic mutant version of Swi5-Sfr1 is defective in both the physical and functional interaction with Rad51. This translated to a defect in DNA repair, with the phosphomimetic mutant yeast strain phenocopying a previously established interaction mutant. Interestingly, a strain in which Sfr1 phosphorylation was blocked also displayed sensitivity to DNA damage. Taken together, we propose that controlled phosphorylation of Sfr1 is important for the role of Swi5-Sfr1 in promoting Rad51-dependent DNA repair.
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Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Schizosaccharomyces pombe
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Reparación del ADN
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Recombinasa Rad51
Idioma:
En
Año:
2023
Tipo del documento:
Article