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Nat Cell Biol
2004 Mar 01;63:260-7. doi: 10.1038/ncb1100.
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Non-proteolytic inactivation of geminin requires CDK-dependent ubiquitination.
Li A
,
Blow JJ
.
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In late mitosis and G1, a complex of the essential initiation proteins Mcm2-7 are assembled onto replication origins to 'license' them for initiation. At other times licensing is inhibited by cyclin-dependent kinases (CDKs) and geminin, thus ensuring that origins fire only once per cell cycle. Here we show that, paradoxically, CDKs are also required to inactivate geminin and activate the licensing system. On exit from metaphase in Xenopus laevis egg extracts, CDK-dependent activation of the anaphase-promoting complex (APC/C) results in the transient polyubiquitination of geminin. This ubiquitination triggers geminin inactivation without requiring ubiquitin-dependent proteolysis, and is essential for replication origins to become licensed. This reveals an unexpected role for CDKs and ubiquitination in activating chromosomal DNA replication.
Bach,
Orchestrating nuclear functions: ubiquitin sets the rhythm.
2003, Pubmed
Bach,
Orchestrating nuclear functions: ubiquitin sets the rhythm.
2003,
Pubmed
Blow,
Preventing re-replication of DNA in a single cell cycle: evidence for a replication licensing factor.
1993,
Pubmed
,
Xenbase
Blow,
Control of chromosomal DNA replication in the early Xenopus embryo.
2001,
Pubmed
,
Xenbase
Blow,
Replication licensing--defining the proliferative state?
2002,
Pubmed
Blow,
A role for the nuclear envelope in controlling DNA replication within the cell cycle.
1988,
Pubmed
,
Xenbase
Blow,
A cdc2-like protein is involved in the initiation of DNA replication in Xenopus egg extracts.
1990,
Pubmed
,
Xenbase
Broek,
Involvement of p34cdc2 in establishing the dependency of S phase on mitosis.
1991,
Pubmed
Chong,
Purification of an MCM-containing complex as a component of the DNA replication licensing system.
1995,
Pubmed
,
Xenbase
Chong,
Characterization of the Xenopus replication licensing system.
1997,
Pubmed
,
Xenbase
Coverley,
Distinct roles for cyclins E and A during DNA replication complex assembly and activation.
2002,
Pubmed
Dahmann,
S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state.
1995,
Pubmed
Diffley,
DNA replication: building the perfect switch.
2001,
Pubmed
Dorée,
From Cdc2 to Cdk1: when did the cell cycle kinase join its cyclin partner?
2002,
Pubmed
Gillespie,
Nucleoplasmin-mediated chromatin remodelling is required for Xenopus sperm nuclei to become licensed for DNA replication.
2000,
Pubmed
,
Xenbase
Gillespie,
Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins.
2001,
Pubmed
,
Xenbase
Hayles,
Temporal order of S phase and mitosis in fission yeast is determined by the state of the p34cdc2-mitotic B cyclin complex.
1994,
Pubmed
Hodgson,
Geminin becomes activated as an inhibitor of Cdt1/RLF-B following nuclear import.
2002,
Pubmed
,
Xenbase
Kubota,
Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor.
1995,
Pubmed
,
Xenbase
Kubota,
Determination of initiation of DNA replication before and after nuclear formation in Xenopus egg cell free extracts.
1993,
Pubmed
,
Xenbase
Luca,
Control of programmed cyclin destruction in a cell-free system.
1989,
Pubmed
Madine,
MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells.
1995,
Pubmed
,
Xenbase
Mahaffey,
Ubiquitin metabolism in cycling Xenopus egg extracts.
1993,
Pubmed
,
Xenbase
Mahaffey,
Evidence that DNA replication is not regulated by ubiquitin-dependent proteolysis in Xenopus egg extract.
2003,
Pubmed
,
Xenbase
Mahbubani,
Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor.
1997,
Pubmed
,
Xenbase
Maiorano,
XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis.
2000,
Pubmed
,
Xenbase
Masui,
Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes.
1971,
Pubmed
McGarry,
Geminin, an inhibitor of DNA replication, is degraded during mitosis.
1998,
Pubmed
,
Xenbase
Meijer,
Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5.
1997,
Pubmed
,
Xenbase
Nguyen,
Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms.
2001,
Pubmed
Nishitani,
The Cdt1 protein is required to license DNA for replication in fission yeast.
2000,
Pubmed
Nishitani,
Control of DNA replication licensing in a cell cycle.
2002,
Pubmed
,
Xenbase
Nishiyama,
A nonproteolytic function of the proteasome is required for the dissociation of Cdc2 and cyclin B at the end of M phase.
2000,
Pubmed
,
Xenbase
Noton,
CDK inactivation is the only essential function of the APC/C and the mitotic exit network proteins for origin resetting during mitosis.
2000,
Pubmed
Peter,
The APC is dispensable for first meiotic anaphase in Xenopus oocytes.
2001,
Pubmed
,
Xenbase
Peters,
The anaphase-promoting complex: proteolysis in mitosis and beyond.
2002,
Pubmed
Petersen,
Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization.
1999,
Pubmed
Prokhorova,
Sequential MCM/P1 subcomplex assembly is required to form a heterohexamer with replication licensing activity.
2000,
Pubmed
,
Xenbase
Saha,
Human CDC6/Cdc18 associates with Orc1 and cyclin-cdk and is selectively eliminated from the nucleus at the onset of S phase.
1998,
Pubmed
Schnell,
Non-traditional functions of ubiquitin and ubiquitin-binding proteins.
2003,
Pubmed
Strausfeld,
Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts.
1996,
Pubmed
,
Xenbase
Su,
Chromosome association of minichromosome maintenance proteins in Drosophila endoreplication cycles.
1998,
Pubmed
Tada,
Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin.
2001,
Pubmed
,
Xenbase
Tunquist,
Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs.
2003,
Pubmed
,
Xenbase
Veselý,
Inhibition of cyclin-dependent kinases by purine analogues.
1994,
Pubmed
,
Xenbase
Wohlschlegel,
Inhibition of eukaryotic DNA replication by geminin binding to Cdt1.
2000,
Pubmed
,
Xenbase
Zachariae,
Whose end is destruction: cell division and the anaphase-promoting complex.
1999,
Pubmed
