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.
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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.
| Type: | Article |
|---|---|
| Title: | Phosphoregulation of DNA repair via the Rad51 auxiliary factor Swi5–Sfr1 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jbc.2023.104929 |
| Publisher version: | http://dx.doi.org/10.1016/j.jbc.2023.104929 |
| Language: | English |
| Additional information: | © 2023 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | DNA repair, genome stability, recombination, Rad51, RecA, Swi5, Sfr1, Rad55, Rad57 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10191618 |
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