Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation

Homology search and strand exchange mediated by Rad51 nucleoprotein filaments are key steps of the homologous recombination process. In budding yeast, Rad52 is the main mediator of Rad51 filament formation, thereby playing an essential role. The current model assumes that Rad51 filament formation re...

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Main Authors: Emilie Ma, Pauline Dupaigne, Laurent Maloisel, Raphaël Guerois, Eric Le Cam, Eric Coïc
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-07-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/32744
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spelling doaj-bb4607bdee234645b4fab35fc4984b0e2021-05-05T16:00:13ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.32744Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formationEmilie Ma0Pauline Dupaigne1Laurent Maloisel2Raphaël Guerois3Eric Le Cam4Eric Coïc5https://orcid.org/0000-0002-9549-8969DRF, IBFJ, iRCM, CEA, Fontenay-aux-Roses, France; Université Paris-Saclay, Paris, FranceUniversité Paris-Saclay, Paris, France; Signalisation, Noyaux et Innovation en Cancérologie, Institut Gustave Roussy, CNRS UMR 8126, Villejuif, France; Université Paris-Sud, Orsay, FranceDRF, IBFJ, iRCM, CEA, Fontenay-aux-Roses, France; Université Paris-Saclay, Paris, FranceUniversité Paris-Saclay, Paris, France; Université Paris-Sud, Orsay, France; DRF, i2BC, LBSR, CEA, Gif-sur-Yvette, FranceUniversité Paris-Saclay, Paris, France; Signalisation, Noyaux et Innovation en Cancérologie, Institut Gustave Roussy, CNRS UMR 8126, Villejuif, France; Université Paris-Sud, Orsay, FranceDRF, IBFJ, iRCM, CEA, Fontenay-aux-Roses, France; Université Paris-Saclay, Paris, FranceHomology search and strand exchange mediated by Rad51 nucleoprotein filaments are key steps of the homologous recombination process. In budding yeast, Rad52 is the main mediator of Rad51 filament formation, thereby playing an essential role. The current model assumes that Rad51 filament formation requires the interaction between Rad52 and Rad51. However, we report here that Rad52 mutations that disrupt this interaction do not affect γ-ray- or HO endonuclease-induced gene conversion frequencies. In vivo and in vitro studies confirmed that Rad51 filaments formation is not affected by these mutations. Instead, we found that Rad52-Rad51 association makes Rad51 filaments toxic in Srs2-deficient cells after exposure to DNA damaging agents, independently of Rad52 role in Rad51 filament assembly. Importantly, we also demonstrated that Rad52 is essential for protecting Rad51 filaments against dissociation by the Srs2 DNA translocase. Our findings open new perspectives in the understanding of the role of Rad52 in eukaryotes.https://elifesciences.org/articles/32744genome stabilityhomologous recombinationRad52Rad51Srs2Saccharomyces cerevisiae
collection DOAJ
language English
format Article
sources DOAJ
author Emilie Ma
Pauline Dupaigne
Laurent Maloisel
Raphaël Guerois
Eric Le Cam
Eric Coïc
spellingShingle Emilie Ma
Pauline Dupaigne
Laurent Maloisel
Raphaël Guerois
Eric Le Cam
Eric Coïc
Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation
eLife
genome stability
homologous recombination
Rad52
Rad51
Srs2
Saccharomyces cerevisiae
author_facet Emilie Ma
Pauline Dupaigne
Laurent Maloisel
Raphaël Guerois
Eric Le Cam
Eric Coïc
author_sort Emilie Ma
title Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation
title_short Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation
title_full Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation
title_fullStr Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation
title_full_unstemmed Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation
title_sort rad52-rad51 association is essential to protect rad51 filaments against srs2, but facultative for filament formation
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2018-07-01
description Homology search and strand exchange mediated by Rad51 nucleoprotein filaments are key steps of the homologous recombination process. In budding yeast, Rad52 is the main mediator of Rad51 filament formation, thereby playing an essential role. The current model assumes that Rad51 filament formation requires the interaction between Rad52 and Rad51. However, we report here that Rad52 mutations that disrupt this interaction do not affect γ-ray- or HO endonuclease-induced gene conversion frequencies. In vivo and in vitro studies confirmed that Rad51 filaments formation is not affected by these mutations. Instead, we found that Rad52-Rad51 association makes Rad51 filaments toxic in Srs2-deficient cells after exposure to DNA damaging agents, independently of Rad52 role in Rad51 filament assembly. Importantly, we also demonstrated that Rad52 is essential for protecting Rad51 filaments against dissociation by the Srs2 DNA translocase. Our findings open new perspectives in the understanding of the role of Rad52 in eukaryotes.
topic genome stability
homologous recombination
Rad52
Rad51
Srs2
Saccharomyces cerevisiae
url https://elifesciences.org/articles/32744
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AT laurentmaloisel rad52rad51associationisessentialtoprotectrad51filamentsagainstsrs2butfacultativeforfilamentformation
AT raphaelguerois rad52rad51associationisessentialtoprotectrad51filamentsagainstsrs2butfacultativeforfilamentformation
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AT ericcoic rad52rad51associationisessentialtoprotectrad51filamentsagainstsrs2butfacultativeforfilamentformation
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