Liang, Pengtao; Lister, Katie; Yates, Luke; Argunhan, Bilge; Zhang, Xiaodong; (2023) Phosphoregulation of DNA repair via the Rad51 auxiliary factor Swi5–Sfr1. Journal of Biological Chemistry , 299 (8) , Article 104929. 10.1016/j.jbc.2023.104929.

Preview

PDF PIIS0021925823019579.pdf - Published Version Download (3MB) | Preview

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.

Download activity - last month

Export as CSVXMLJSON

Download activity - last 12 months

Export as CSVJSONXML

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item