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XB-ART-47109
Nat Commun January 1, 2013; 4 1850.
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SUMO2/3 modification of cyclin E contributes to the control of replication origin firing.

Bonne-Andrea C , Kahli M , Mechali F , Lemaitre JM , Bossis G , Coux O .


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.

PubMed ID: 23673635
PMC ID: PMC3674260
Article link: Nat Commun


Species referenced: Xenopus laevis
Genes referenced: atm atr cdc6 cdk2 ctrl rnf4 rpa1 rpa2 sae1 sumo1 sumo2 sumo3 ube2i


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References [+] :
Azuma, SUMO-2/3 regulates topoisomerase II in mitosis. 2003, Pubmed, Xenbase