SUMO2/3 modification of cyclin E contributes to the control of replication origin firing

Catherine Bonne-Andrea (), Malik Kahli, Francisca Mechali, Jean-Marc Lemaitre, Guillaume Bossis and Olivier Coux
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Catherine Bonne-Andrea: Centre de Recherche de Biochimie Macromoléculaire (CRBM), CNRS UMR5237, University Montpellier I and II, 1919 route de Mende, 34293 Montpellier Cedex 05, France
Malik Kahli: Institut de Génomique Fonctionnelle (IGF), CNRS UMR5203, University Montpellier I and II, 141 rue de la Cardonille, 34094 Montpellier Cedex 05, France
Francisca Mechali: Centre de Recherche de Biochimie Macromoléculaire (CRBM), CNRS UMR5237, University Montpellier I and II, 1919 route de Mende, 34293 Montpellier Cedex 05, France
Jean-Marc Lemaitre: Institut de Génomique Fonctionnelle (IGF), CNRS UMR5203, University Montpellier I and II, 141 rue de la Cardonille, 34094 Montpellier Cedex 05, France
Guillaume Bossis: Institut de Génétique Moléculaire Montpellier (IGMM), CNRS UMR5535, University Montpellier I and II, 1919 route de Mende, 34293 Montpellier Cedex 05, France
Olivier Coux: Centre de Recherche de Biochimie Macromoléculaire (CRBM), CNRS UMR5237, University Montpellier I and II, 1919 route de Mende, 34293 Montpellier Cedex 05, France

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: Abstract The small ubiquitin-like modifier (SUMO) pathway is essential for the maintenance of genome stability. We investigated its possible involvement in the control of DNA replication during S phase by using the Xenopus cell-free system. Here we show that the SUMO pathway is critical to limit the number and, thus, the density of replication origins that are activated in early S phase. We identified cyclin E, which regulates cyclin-dependent kinase 2 (Cdk2) to trigger origin firing, as an S-phase substrate of this pathway. We show that cyclin E is dynamically and highly conjugated to SUMO2/3 on chromatin, independently of Cdk2 activity and origin activation. Moreover, cyclin E is the predominant SUMO2/3 target on chromatin in early S phase, as cyclin E depletion abolishes, while its readdition restores, the SUMO2/3 signal. Together, our data indicate that cyclin E SUMOylation is important for controlling origin firing once the cyclin E–Cdk2 complex is recruited onto replication origins.

Date: 2013
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DOI: 10.1038/ncomms2875

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