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

Author

Listed:
  • David Walter

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen)

  • Saskia Hoffmann

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen)

  • Eirini-Stavroula Komseli

    (School of Medicine, University of Athens)

  • Juri Rappsilber

    (Wellcome Trust Centre for Cell Biology, University of Edinburgh
    Institute of Biotechnology, Technische Universität Berlin)

  • Vassilis Gorgoulis

    (School of Medicine, University of Athens
    Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre)

  • Claus Storgaard Sørensen

    (Biotech Research and Innovation Centre (BRIC), University of Copenhagen)

Abstract

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.

Suggested Citation

  • David Walter & Saskia Hoffmann & Eirini-Stavroula Komseli & Juri Rappsilber & Vassilis Gorgoulis & Claus Storgaard Sørensen, 2016. "SCFCyclin F-dependent degradation of CDC6 suppresses DNA re-replication," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10530
    DOI: 10.1038/ncomms10530
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