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

  1. Emilie Ma
  2. Pauline Dupaigne
  3. Laurent Maloisel
  4. Raphaël Guerois
  5. Eric Le Cam
  6. Eric Coïc  Is a corresponding author
  1. CEA-Université Paris Saclay, France
  2. Institut Gustave Roussy, France

Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Emilie Ma

    Institut de Biologie François Jacob, IRCM, CEA-Université Paris Saclay, Fontenay-aux-Roses, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Pauline Dupaigne

    Signalisation, Noyaux et Innovation en Cancérologie, Institut Gustave Roussy, Villejuif, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Laurent Maloisel

    Institut de Biologie François Jacob, IRCM, CEA-Université Paris Saclay, Fontenay-aux-Roses, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Raphaël Guerois

    CEA-Université Paris Saclay, Gif-sur-Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Eric Le Cam

    Signalisation, Noyaux et Innovation en Cancérologie, Institut Gustave Roussy, Villejuif, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Eric Coïc

    Institut de Biologie François Jacob, IRCM, CEA-Université Paris Saclay, Fontenay-aux-Roses, France
    For correspondence
    eric.coic@cea.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9549-8969

Funding

Commissariat à l'Énergie Atomique et aux Énergies Alternatives (Recurrent funding)

  • Raphaël Guerois
  • Eric Coïc

Centre National de la Recherche Scientifique (Recurrent funding)

  • Eric Le Cam

Fondation ARC pour la Recherche sur le Cancer (SFI20121205689)

  • Eric Coïc

Ligue Contre le Cancer (2015-16)

  • Eric Coïc

Agence Nationale de la Recherche (ANR-15-CE11-0008-01)

  • Raphaël Guerois

Region Ile-de-France (DIM Nano-K No F13012333)

  • Eric Le Cam

Fondation ARC pour la Recherche sur le Cancer (PJA 20141201772)

  • Eric Coïc

Ligue Contre le Cancer (2016-2017)

  • Eric Le Cam

Agence Nationale de la Recherche (ANR-13-BSV8-0022)

  • Eric Le Cam

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Andrés Aguilera, CABIMER, Universidad de Sevilla, Spain

Publication history

  1. Received: October 12, 2017
  2. Accepted: June 30, 2018
  3. Accepted Manuscript published: July 9, 2018 (version 1)
  4. Version of Record published: July 23, 2018 (version 2)

Copyright

© 2018, Ma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Emilie Ma
  2. Pauline Dupaigne
  3. Laurent Maloisel
  4. Raphaël Guerois
  5. Eric Le Cam
  6. Eric Coïc
(2018)
Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation
eLife 7:e32744.
https://doi.org/10.7554/eLife.32744

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