Rad54 and Rdh54 occupy spatially and functionally distinct sites within the Rad51-ssDNA presynaptic complex.


Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
15 10 2020
Historique:
received: 21 05 2020
revised: 13 07 2020
accepted: 29 07 2020
pubmed: 14 8 2020
medline: 15 4 2021
entrez: 14 8 2020
Statut: ppublish

Résumé

Rad54 and Rdh54 are closely related ATP-dependent motor proteins that participate in homologous recombination (HR). During HR, these enzymes functionally interact with the Rad51 presynaptic complex (PSC). Despite their importance, we know little about how they are organized within the PSC, or how their organization affects PSC function. Here, we use single-molecule optical microscopy and genetic analysis of chimeric protein constructs to evaluate the binding distributions of Rad54 and Rdh54 within the PSC. We find that Rad54 and Rdh54 have distinct binding sites within the PSC, which allow these proteins to act cooperatively as DNA sequences are aligned during homology search. Our data also reveal that Rad54 must bind to a specific location within the PSC, whereas Rdh54 retains its function in the repair of MMS-induced DNA damage even when recruited to the incorrect location. These findings support a model in which the relative binding sites of Rad54 and Rdh54 help to define their functions during mitotic HR.

Identifiants

pubmed: 32790929
doi: 10.15252/embj.2020105705
pmc: PMC7560196
doi:

Substances chimiques

Cell Cycle Proteins 0
DNA, Single-Stranded 0
DNA-Binding Proteins 0
Hed1 protein, S cerevisiae 0
Recombinant Proteins 0
Saccharomyces cerevisiae Proteins 0
RAD51 protein, S cerevisiae EC 2.7.7.-
Rad51 Recombinase EC 2.7.7.-
RAD54 protein, S cerevisiae EC 3.6.1.-
DNA Helicases EC 3.6.4.-
DNA Topoisomerases EC 5.99.1.-
RDH54 protein, S cerevisiae EC 5.99.1.-
DNA Repair Enzymes EC 6.5.1.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e105705

Subventions

Organisme : Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation)
ID : DRG 2310-17
Organisme : NCI NIH HHS
ID : P01 CA092584
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM118026
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA054174
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES007061
Pays : United States
Organisme : NSF|BIO|Division of Molecular and Cellular Biosciences (MCB)
ID : MCB1154511
Organisme : NCI NIH HHS
ID : R35 CA241801
Pays : United States

Informations de copyright

© 2020 The Authors.

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Auteurs

J Brooks Crickard (JB)

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

Youngho Kwon (Y)

Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Patrick Sung (P)

Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Eric C Greene (EC)

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

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Classifications MeSH