SCFCyclin F-dependent degradation of CDC6 suppresses DNA re-replication
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SCFCyclin F-dependent degradation of CDC6 suppresses DNA re-replication. / Walter, David; Hoffmann, Saskia; Komseli, Eirini-Stavroula; Rappsilber, Juri; Gorgoulis, Vassilis; Sørensen, Claus Storgaard.
I: Nature Communications, Bind 7, 10530, 2016.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - SCFCyclin F-dependent degradation of CDC6 suppresses DNA re-replication
AU - Walter, David
AU - Hoffmann, Saskia
AU - Komseli, Eirini-Stavroula
AU - Rappsilber, Juri
AU - Gorgoulis, Vassilis
AU - Sørensen, Claus Storgaard
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Amino Acid Motifs
KW - Cell Cycle
KW - Cell Cycle Proteins
KW - Cyclins
KW - DNA Replication
KW - Humans
KW - Nuclear Proteins
KW - Protein Binding
KW - Proteolysis
KW - SKP Cullin F-Box Protein Ligases
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/ncomms10530
DO - 10.1038/ncomms10530
M3 - Journal article
C2 - 26818844
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 10530
ER -
ID: 165717375