Redox controls RecA protein activity via reversible oxidation of its methionine residues
- University of Wisconsin-Madison, United States
- Aix-Marseille University, CNRS, France
- Université Catholique de Louvain, Belgium
- Universidad de Sevilla, Spain
- Institut Pasteur, France
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).
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Redox controls RecA protein activity via reversible oxidation of its methionine residuesDryad Digital Repository, doi:10.5061/dryad.zpc866t78.
Article and author information
Author details
Angela Mérida-Floriano
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
- Stephen C Kowalczykowski, University of California, Davis, United States
Publication history
- Received: October 6, 2020
- Accepted: February 18, 2021
- Accepted Manuscript published: February 19, 2021 (version 1)
- Accepted Manuscript updated: February 23, 2021 (version 2)
- 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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