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

Research output: Contribution to journalJournal articleResearchpeer-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 SCF(Cyclin 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 SCF(Cyclin F)-mediated mechanism required for precise once per cell cycle replication.

Original languageEnglish
Article number10530
JournalNature Communications
Number of pages10
Publication statusPublished - 2016

    Research areas

  • Amino Acid Motifs, Cell Cycle, Cell Cycle Proteins, Cyclins, DNA Replication, Humans, Nuclear Proteins, Protein Binding, Proteolysis, SKP Cullin F-Box Protein Ligases, Journal Article, Research Support, Non-U.S. Gov't

ID: 165717375