title: SUMO2/3 modification of cyclin E contributes to the control of replication origin firing.
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.
authors.affiliation: Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR5237, University Montpellier I and II, 1919 route de Mende, 34293 Montpellier Cedex 05, France. catherine.bonne-andrea@crbm.cnrs.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Bonne-Andrea
authors.forename: Malik
authors.initials: M
authors.lastname: Kahli
authors.forename: Francisca
authors.initials: F
authors.lastname: Mechali
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lemaitre
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bossis
authors.forename: Olivier
authors.initials: O
authors.lastname: Coux
mesh_terms: D000818:Animals; D002457:Cell Extracts; D002843:Chromatin / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D004261:DNA Replication; D006801:Humans; D010063:Ovum / Q000378:metabolism; D018741:Replication Origin; D016196:S Phase; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D002457:Cell Extracts; D002843:Chromatin; D019927:Cyclin E; D025841:Small Ubiquitin-Related Modifier Proteins; D029867:Xenopus Proteins; D044763:Ubiquitin-Conjugating Enzymes; D051357:Cyclin-Dependent Kinase 2; D000098843:Ubiquitin-Conjugating Enzyme UBC9