Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Genes Dev
2002 May 15;1610:1182-94. doi: 10.1101/gad.985302.
Show Gene links
Show Anatomy links
Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication.
You Z, Harvey K, Kong L, Newport J.
???displayArticle.abstract??? CDK2 activity is regulated by phosphorylation/dephosphorylation, subcellular localization, cyclin levels, and cyclin dependent kinase inhibitors (CKIs). Using Xenopus egg extracts, we find that degradation of Xic1, a Xenopus p21(cip1)/p27(kip1) family member, is coupled to initiation of DNA replication. Xic1 turnover requires the formation of a prereplication complex (pre-RC). Additionally, downstream initiation factors including CDK2, Cdc7, and Cdc45, but not RPA or DNA polymerase alpha, are necessary for activating the degradation system. Xic1 degradation is attenuated following completion of DNA replication. Unlike degradation of p27(kip1) in mammalian cells, CDK2 activity is not directly involved in Xic1 degradation and interactions between Xic1 and CDK2/cyclin E are dispensable for Xic1 turnover. Interestingly, a C-terminal region (162-192) of Xic1 is essential and apparently sufficient for triggering Xic1 ubiquitination prior to degradation. These observations demonstrate that a direct link exists between DNA replication and CKI degradation.
???displayArticle.pubmedLink???
12023298 ???displayArticle.pmcLink???PMC186278 ???displayArticle.link???Genes Dev ???displayArticle.grants???[+]
Aparicio,
Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
1997, Pubmed
Aparicio,
Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.
1997,
Pubmed Blow,
Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs.
1986,
Pubmed
,
Xenbase Bousset,
The Cdc7 protein kinase is required for origin firing during S phase.
1998,
Pubmed Burgers,
Saccharomyces cerevisiae replication factor C. II. Formation and activity of complexes with the proliferating cell nuclear antigen and with DNA polymerases delta and epsilon.
1991,
Pubmed Chuang,
Regulation of nuclear transport and degradation of the Xenopus cyclin-dependent kinase inhibitor, p27Xic1.
2001,
Pubmed
,
Xenbase Coleman,
The Xenopus Cdc6 protein is essential for the initiation of a single round of DNA replication in cell-free extracts.
1996,
Pubmed
,
Xenbase Dahmann,
S-phase-promoting cyclin-dependent kinases prevent re-replication by inhibiting the transition of replication origins to a pre-replicative state.
1995,
Pubmed DePamphilis,
Initiation of DNA replication in eukaryotic chromosomes.
1998,
Pubmed Deshaies,
Phosphorylation and proteolysis: partners in the regulation of cell division in budding yeast.
1997,
Pubmed Diffley,
Once and only once upon a time: specifying and regulating origins of DNA replication in eukaryotic cells.
1996,
Pubmed Donaldson,
CLB5-dependent activation of late replication origins in S. cerevisiae.
1998,
Pubmed Donaldson,
Cdc7 is required throughout the yeast S phase to activate replication origins.
1998,
Pubmed Dutta,
Initiation of DNA replication in eukaryotic cells.
1997,
Pubmed Fang,
Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes.
1991,
Pubmed
,
Xenbase Furstenthal,
Triggering ubiquitination of a CDK inhibitor at origins of DNA replication.
2001,
Pubmed
,
Xenbase Guadagno,
Cdk2 kinase is required for entry into mitosis as a positive regulator of Cdc2-cyclin B kinase activity.
1996,
Pubmed
,
Xenbase Hinchcliffe,
Requirement of Cdk2-cyclin E activity for repeated centrosome reproduction in Xenopus egg extracts.
1999,
Pubmed
,
Xenbase Howe,
A developmental timer regulates degradation of cyclin E1 at the midblastula transition during Xenopus embryogenesis.
1996,
Pubmed
,
Xenbase Hua,
A role for Cdk2 kinase in negatively regulating DNA replication during S phase of the cell cycle.
1997,
Pubmed
,
Xenbase Kamura,
Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase.
1999,
Pubmed King,
How proteolysis drives the cell cycle.
1996,
Pubmed Lacey,
Cyclin-dependent kinase control of centrosome duplication.
1999,
Pubmed
,
Xenbase Leatherwood,
Emerging mechanisms of eukaryotic DNA replication initiation.
1998,
Pubmed Lee,
Studies on the activator 1 protein complex, an accessory factor for proliferating cell nuclear antigen-dependent DNA polymerase delta.
1991,
Pubmed Lee,
Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1.
1990,
Pubmed Ma,
Cell cycle-regulated phosphorylation of p220(NPAT) by cyclin E/Cdk2 in Cajal bodies promotes histone gene transcription.
2000,
Pubmed Maiorano,
XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis.
2000,
Pubmed
,
Xenbase Malek,
A mouse knock-in model exposes sequential proteolytic pathways that regulate p27Kip1 in G1 and S phase.
2001,
Pubmed Matsumoto,
Cyclin-dependent kinase 2 (Cdk2) is required for centrosome duplication in mammalian cells.
1999,
Pubmed Meraldi,
Centrosome duplication in mammalian somatic cells requires E2F and Cdk2-cyclin A.
1999,
Pubmed Mimura,
Xenopus Cdc45-dependent loading of DNA polymerase alpha onto chromatin under the control of S-phase Cdk.
1998,
Pubmed
,
Xenbase Mimura,
Central role for cdc45 in establishing an initiation complex of DNA replication in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase Montagnoli,
Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation.
1999,
Pubmed Morgan,
Cyclin-dependent kinases: engines, clocks, and microprocessors.
1997,
Pubmed Nakayama,
Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication.
2000,
Pubmed Newport,
Nuclear reconstitution in vitro: stages of assembly around protein-free DNA.
1987,
Pubmed
,
Xenbase Nguyen,
Cell-free degradation of p27(kip1), a G1 cyclin-dependent kinase inhibitor, is dependent on CDK2 activity and the proteasome.
1999,
Pubmed Nishizawa,
Phosphorylation of sic1, a cyclin-dependent kinase (Cdk) inhibitor, by Cdk including Pho85 kinase is required for its prompt degradation.
1998,
Pubmed Owens,
CDC45 is required in conjunction with CDC7/DBF4 to trigger the initiation of DNA replication.
1997,
Pubmed Podust,
Calf thymus RF-C as an essential component for DNA polymerase delta and epsilon holoenzymes function.
1992,
Pubmed Rodier,
p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis.
2001,
Pubmed Schneider,
Linkage of replication to start by the Cdk inhibitor Sic1.
1996,
Pubmed Schwob,
The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
1994,
Pubmed Seol,
Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34.
1999,
Pubmed Sheaff,
End of the line: proteolytic degradation of cyclin-dependent kinase inhibitors.
1996,
Pubmed Sheehan,
Steps in the assembly of replication-competent nuclei in a cell-free system from Xenopus eggs.
1988,
Pubmed
,
Xenbase Sherr,
CDK inhibitors: positive and negative regulators of G1-phase progression.
1999,
Pubmed Skowyra,
Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1.
1999,
Pubmed Skowyra,
F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex.
1997,
Pubmed Smythe,
Systems for the study of nuclear assembly, DNA replication, and nuclear breakdown in Xenopus laevis egg extracts.
1991,
Pubmed
,
Xenbase Stillman,
Cell cycle control of DNA replication.
1996,
Pubmed Strausfeld,
Both cyclin A and cyclin E have S-phase promoting (SPF) activity in Xenopus egg extracts.
1996,
Pubmed
,
Xenbase Su,
Cloning and characterization of the Xenopus cyclin-dependent kinase inhibitor p27XIC1.
1995,
Pubmed
,
Xenbase Swanson,
Nuclear accumulation of cyclin E/Cdk2 triggers a concentration-dependent switch for the destruction of p27Xic1.
2000,
Pubmed
,
Xenbase Tanaka,
Association of RPA with chromosomal replication origins requires an Mcm protein, and is regulated by Rad53, and cyclin- and Dbf4-dependent kinases.
1998,
Pubmed Tercero,
DNA synthesis at individual replication forks requires the essential initiation factor Cdc45p.
2000,
Pubmed Tsurimoto,
Multiple replication factors augment DNA synthesis by the two eukaryotic DNA polymerases, alpha and delta.
1989,
Pubmed Tsvetkov,
p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27.
1999,
Pubmed Tyers,
The cyclin-dependent kinase inhibitor p40SIC1 imposes the requirement for Cln G1 cyclin function at Start.
1996,
Pubmed Verma,
Phosphorylation of Sic1p by G1 Cdk required for its degradation and entry into S phase.
1997,
Pubmed Verma,
SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities.
1997,
Pubmed Vlach,
Phosphorylation-dependent degradation of the cyclin-dependent kinase inhibitor p27.
1997,
Pubmed Walker,
Role for cyclin A in the dependence of mitosis on completion of DNA replication.
1991,
Pubmed
,
Xenbase Walter,
Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase alpha.
2000,
Pubmed
,
Xenbase Walter,
Regulated chromosomal DNA replication in the absence of a nucleus.
1998,
Pubmed
,
Xenbase Yew,
Proteolysis and DNA replication: the CDC34 requirement in the Xenopus egg cell cycle.
1997,
Pubmed
,
Xenbase Zhao,
NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription.
2000,
Pubmed Zou,
Formation of a preinitiation complex by S-phase cyclin CDK-dependent loading of Cdc45p onto chromatin.
1998,
Pubmed Zou,
Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p at replication origins controlled by S-phase cyclin-dependent kinases and Cdc7p-Dbf4p kinase.
2000,
Pubmed
