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

David Walter, Saskia Hoffmann, Eirini-Stavroula Komseli, Juri Rappsilber, Vassilis Gorgoulis and Claus Storgaard Sørensen ()
Additional contact information
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
Vassilis Gorgoulis: School of Medicine, University of Athens
Claus Storgaard Sørensen: Biotech Research and Innovation Centre (BRIC), University of Copenhagen

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10530 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10530

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10530

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().