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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: The Rad51 paralog complex Rad55-Rad57 acts as a molecular chaperone during homologous recombination.

Authors: Roy, Upasana; Kwon, Youngho; Marie, Lea; Symington, Lorraine; Sung, Patrick; Lisby, Michael; Greene, Eric C

Published In Mol Cell, (2021 03 04)

Abstract: Homologous recombination (HR) is essential for maintenance of genome integrity. Rad51 paralogs fulfill a conserved but undefined role in HR, and their mutations are associated with increased cancer risk in humans. Here, we use single-molecule imaging to reveal that the Saccharomyces cerevisiae Rad51 paralog complex Rad55-Rad57 promotes assembly of Rad51 recombinase filament through transient interactions, providing evidence that it acts like a classical molecular chaperone. Srs2 is an ATP-dependent anti-recombinase that downregulates HR by actively dismantling Rad51 filaments. Contrary to the current model, we find that Rad55-Rad57 does not physically block the movement of Srs2. Instead, Rad55-Rad57 promotes rapid re-assembly of Rad51 filaments after their disruption by Srs2. Our findings support a model in which Rad51 is in flux between free and single-stranded DNA (ssDNA)-bound states, the rate of which is controlled dynamically though the opposing actions of Rad55-Rad57 and Srs2.

PubMed ID: 33421364 Exiting the NIEHS site

MeSH Terms: Adenosine Triphosphatases/genetics*; Adenosine Triphosphatases/metabolism; Binding Sites; DNA Helicases/genetics*; DNA Helicases/metabolism; DNA Repair Enzymes/genetics*; DNA Repair Enzymes/metabolism; DNA, Fungal/genetics; DNA, Fungal/metabolism; DNA, Single-Stranded/genetics; DNA, Single-Stranded/metabolism; DNA-Binding Proteins/genetics*; DNA-Binding Proteins/metabolism; Gene Expression Regulation, Fungal*; Genes, Reporter; Green Fluorescent Proteins/genetics; Green Fluorescent Proteins/metabolism; Homologous Recombination*; Luminescent Proteins/genetics; Luminescent Proteins/metabolism; Molecular Chaperones/genetics; Molecular Chaperones/metabolism; Mutation; Protein Binding; Rad51 Recombinase/genetics*; Rad51 Recombinase/metabolism; Saccharomyces cerevisiae Proteins/genetics*; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/genetics*; Saccharomyces cerevisiae/metabolism; Signal Transduction; Single Molecule Imaging

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