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

Author

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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
    Present address: Institut de Biologie de l’Ecole Normale Supérieure (IBENS), CNRS UMR8197, Inserm U1024, 46 rue d’Ulm, 75230 Paris 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)

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.

Suggested Citation

  • Catherine Bonne-Andrea & Malik Kahli & Francisca Mechali & Jean-Marc Lemaitre & Guillaume Bossis & Olivier Coux, 2013. "SUMO2/3 modification of cyclin E contributes to the control of replication origin firing," Nature Communications, Nature, vol. 4(1), pages 1-8, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2875
    DOI: 10.1038/ncomms2875
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