1. Microbiology and Infectious Disease

Redox controls RecA protein activity via reversible oxidation of its methionine residues

  1. Camille Henry
  2. Laurent Loiseau
  3. Alexandra Vergnes
  4. Didier Vertommen
  5. Angela Mérida-Floriano
  6. Sindhu Chitteni-Pattu
  7. Elizabeth A Wood
  8. Josep Casadesús
  9. Michael M Cox
  10. Frédéric Barras  Is a corresponding author
  11. Benjamin Ezraty  Is a corresponding author
  1. University of Wisconsin-Madison, United States
  2. Aix-Marseille University, CNRS, France
  3. Université Catholique de Louvain, Belgium
  4. Universidad de Sevilla, Spain
  5. Institut Pasteur, France
https://doi.org/10.7554/eLife.63747
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  1. Camille Henry
  2. Laurent Loiseau
  3. Alexandra Vergnes
  4. Didier Vertommen
  5. Angela Mérida-Floriano
  6. Sindhu Chitteni-Pattu
  7. Elizabeth A Wood
  8. Josep Casadesús
  9. Michael M Cox
  10. Frédéric Barras
  11. Benjamin Ezraty
(2021)
Redox controls RecA protein activity via reversible oxidation of its methionine residues
eLife 10:e63747.
https://doi.org/10.7554/eLife.63747
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Abstract

Reactive oxygen species (ROS) cause damage to DNA and proteins. Here we report that the RecA recombinase is itself oxidized by ROS. Genetic and biochemical analyses revealed that oxidation of RecA altered its DNA repair and DNA recombination activities. Mass spectrometry analysis showed that exposure to ROS converted 4 out of 9 Met residues of RecA to methionine sulfoxide. Mimicking oxidation of Met35 by changing it for Gln caused complete loss of function whereas mimicking oxidation of Met164 resulted in constitutive SOS activation and loss of recombination activity. Yet, all ROS-induced alterations of RecA activity were suppressed by methionine sulfoxide reductases MsrA and MsrB. These findings indicate that under oxidative stress, MsrA/B is needed for RecA homeostasis control. The implication is that, besides damaging DNA structure directly, ROS prevent repair of DNA damage by hampering RecA activity.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided in Dryad (doi:10.5061/dryad.zpc866t78).

The following data sets were generated

Article and author information

Author details

  1. Camille Henry

    Departement of Biochemistry, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Laurent Loiseau

    Laboratoire de Chimie Bactérienne, Aix-Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Alexandra Vergnes

    Laboratoire de Chimie Bactérienne, Aix-Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.

  4. Didier Vertommen

    Protein Phosphorylation Unit, de Duve Institute,, Université Catholique de Louvain, Brussels, Belgium
    Competing interests
    The authors declare that no competing interests exist.

  5. Angela Mérida-Floriano

    Departamento de Genética, Universidad de Sevilla, Sevilla, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9650-7759

  6. Sindhu Chitteni-Pattu

    Departement of Biochemistry, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Elizabeth A Wood

    Department of Biochemistry, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Josep Casadesús

    Departamento de Genética, Universidad de Sevilla, Sevilla, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2308-293X

  9. Michael M Cox

    Department of Biochemistry, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3606-5722

  10. Frédéric Barras

    Institut Pasteur, Paris, France
    For correspondence
    frederic.barras@pasteur.fr
    Competing interests
    The authors declare that no competing interests exist.

  11. Benjamin Ezraty

    Laboratoire de Chimie Bactérienne, Aix-Marseille University, CNRS, Marseille, France
    For correspondence
    ezraty@imm.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3818-6907

Funding

Agence Nationale de la Recherche (ANR-METOXIC)

  • Benjamin Ezraty

Centre National de la Recherche Scientifique (PICS-PROTOX)

  • Benjamin Ezraty

Agence Nationale de la Recherche (ANR-10-LABX-62-IBEID)

  • Frédéric Barras

Fondation pour la Recherche Médicale

  • Camille Henry

Aix-Marseille Université (AMidex)

  • Camille Henry

National Institute of General Medical Sciences (GM32335)

  • Michael M Cox

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

Reviewing Editor

  1. Stephen C Kowalczykowski, University of California, Davis, United States

Publication history

  1. Received: October 6, 2020
  2. Accepted: February 18, 2021
  3. Accepted Manuscript published: February 19, 2021 (version 1)
  4. Accepted Manuscript updated: February 23, 2021 (version 2)
  5. Version of Record published: March 8, 2021 (version 3)

Copyright

© 2021, Henry 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. Camille Henry
  2. Laurent Loiseau
  3. Alexandra Vergnes
  4. Didier Vertommen
  5. Angela Mérida-Floriano
  6. Sindhu Chitteni-Pattu
  7. Elizabeth A Wood
  8. Josep Casadesús
  9. Michael M Cox
  10. Frédéric Barras
  11. Benjamin Ezraty
(2021)
Redox controls RecA protein activity via reversible oxidation of its methionine residues
eLife 10:e63747.
https://doi.org/10.7554/eLife.63747

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