The separation pin distinguishes the pro- and anti-recombinogenic functions of Saccharomyces cerevisiae Srs2.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
08 Dec 2023
Historique:
received: 22 03 2023
accepted: 23 11 2023
medline: 9 12 2023
pubmed: 9 12 2023
entrez: 8 12 2023
Statut: epublish

Résumé

Srs2 is an Sf1a helicase that helps maintain genome stability in Saccharomyces cerevisiae through its ability to regulate homologous recombination. Srs2 downregulates HR by stripping Rad51 from single-stranded DNA, and Srs2 is also thought to promote synthesis-dependent strand annealing by unwinding D-loops. However, it has not been possible to evaluate the relative contributions of these two distinct activities to any aspect of recombination. Here, we used a structure-based approach to design an Srs2 separation-of-function mutant that can dismantle Rad51-ssDNA filaments but is incapable of disrupting D-loops, allowing us to assess the relative contributions of these pro- and anti-recombinogenic functions. We show that this separation-of-function mutant phenocopies wild-type SRS2 in vivo, suggesting that the ability of Srs2 to remove Rad51 from ssDNA is its primary role during HR.

Identifiants

pubmed: 38065943
doi: 10.1038/s41467-023-43918-4
pii: 10.1038/s41467-023-43918-4
pmc: PMC10709652
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8144

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01CA236606
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R35GM118026

Informations de copyright

© 2023. The Author(s).

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Auteurs

Aviv Meir (A)

Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, 10032, USA.

Vivek B Raina (VB)

Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, 10032, USA.

Carly E Rivera (CE)

Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, 10032, USA.

Léa Marie (L)

Department of Microbiology & Immunology, Columbia University, New York, NY, 10032, USA.
Institute of Pharmacology and Structural Biology (IPBS), French National Centre for Scientific Research (CNRS), Université Toulouse III, Toulouse, France.

Lorraine S Symington (LS)

Department of Microbiology & Immunology, Columbia University, New York, NY, 10032, USA.
Department of Genetics & Development, Columbia University, New York, NY, 10032, USA.

Eric C Greene (EC)

Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY, 10032, USA. ecg2108@cumc.columbia.edu.

Classifications MeSH