SCFCyclin F-dependent degradation of CDC6 suppresses DNA re-replication

David Walter, Saskia Hoffmann, Eirini Stavroula Komseli, Juri Rappsilber, Vassilis Gorgoulis, Claus Storgaard Sørensen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Maintenance of genome stability requires that DNA is replicated precisely once per cell cycle. This is believed to be achieved by limiting replication origin licensing and thereby restricting the firing of each replication origin to once per cell cycle. CDC6 is essential for eukaryotic replication origin licensing, however, it is poorly understood how CDC6 activity is constrained in higher eukaryotes. Here we report that the SCFCyclin F ubiquitin ligase complex prevents DNA re-replication by targeting CDC6 for proteasomal degradation late in the cell cycle. We show that CDC6 and Cyclin F interact through defined sequence motifs that promote CDC6 ubiquitylation and degradation. Absence of Cyclin F or expression of a stable mutant of CDC6 promotes re-replication and genome instability in cells lacking the CDT1 inhibitor Geminin. Together, our work reveals a novel SCFCyclin F-mediated mechanism required for precise once per cell cycle replication.

Original languageEnglish
Article number10530
JournalNature Communications
Publication statusPublished - 28 Jan 2016


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