XB-ART-19426
J Cell Biol
1995 Aug 01;1304:755-69.
Show Gene links
Show Anatomy links
Early events in DNA replication require cyclin E and are blocked by p21CIP1.
Jackson PK
,
Chevalier S
,
Philippe M
,
Kirschner MW
.
???displayArticle.abstract???
Using immunodepletion of cyclin E and the inhibitor protein p21WAF/CIP1, we demonstrate that the cyclin E protein, in association with Cdk2, is required for the elongation phase of replication on single-stranded substrates. Although cyclin E/Cdk2 is likely to be the major target by which p21 inhibits the initiation of sperm DNA replication, p21 can inhibit single-stranded replication through a mechanism dependent on PCNA. While the cyclin E/Cdk2 complex appears to have a role in the initiation of DNA replication, another Cdk kinase, possibly cyclin A/Cdk, may be involved in a later step controlling the switch from initiation to elongation. The provision of a large maternal pool of cyclin E protein shows that regulators of replication are constitutively present, which explains the lack of a protein synthesis requirement for replication in the early embryonic cell cycle.
???displayArticle.pubmedLink??? 7642695
???displayArticle.pmcLink??? PMC2199964
???displayArticle.grants??? [+]
GM39023-05 NIGMS NIH HHS
Species referenced: Xenopus
Genes referenced: cdk2 cdkn1a nsg1 pcna
References [+] :
Adachi,
Study of the cell cycle-dependent assembly of the DNA pre-replication centres in Xenopus egg extracts.
1994, Pubmed,
Xenbase
Adachi, Study of the cell cycle-dependent assembly of the DNA pre-replication centres in Xenopus egg extracts. 1994, Pubmed , Xenbase
Adachi, Identification of nuclear pre-replication centers poised for DNA synthesis in Xenopus egg extracts: immunolocalization study of replication protein A. 1992, Pubmed , Xenbase
Amon, Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle. 1994, Pubmed
Blow, Nuclei act as independent and integrated units of replication in a Xenopus cell-free DNA replication system. 1987, Pubmed , Xenbase
Blow, Initiation of DNA replication in nuclei and purified DNA by a cell-free extract of Xenopus eggs. 1986, Pubmed , Xenbase
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
Brizuela, p13suc1 acts in the fission yeast cell division cycle as a component of the p34cdc2 protein kinase. 1987, Pubmed
Cardoso, Reversal of terminal differentiation and control of DNA replication: cyclin A and Cdk2 specifically localize at subnuclear sites of DNA replication. 1993, Pubmed
Chen, Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. 1995, Pubmed , Xenbase
Cox, DNA replication in cell-free extracts from Xenopus eggs is prevented by disrupting nuclear envelope function. 1992, Pubmed , Xenbase
Draetta, Mammalian G1 cyclins. 1994, Pubmed
Dulić, Association of human cyclin E with a periodic G1-S phase protein kinase. 1992, Pubmed
el-Deiry, WAF1, a potential mediator of p53 tumor suppression. 1993, Pubmed
Fang, Distinct roles of cdk2 and cdc2 in RP-A phosphorylation during the cell cycle. 1993, Pubmed , Xenbase
Fang, Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes. 1991, Pubmed , Xenbase
Flores-Rozas, Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme. 1994, Pubmed
Girard, Cyclin A is required for the onset of DNA replication in mammalian fibroblasts. 1991, Pubmed
Gu, Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit. 1993, Pubmed
Harper, The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. 1993, Pubmed
Heichman, Rules to replicate by. 1994, Pubmed
Hinds, Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. 1992, Pubmed
Howe, Identification of a developmental timer regulating the stability of embryonic cyclin A and a new somatic A-type cyclin at gastrulation. 1995, Pubmed , Xenbase
Hunter, Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. 1994, Pubmed
Hutchison, Periodic DNA synthesis in cell-free extracts of Xenopus eggs. 1987, Pubmed , Xenbase
Hutchison, DNA replication and cell cycle control in Xenopus egg extracts. 1989, Pubmed , Xenbase
Ito, Sequence-specific DNA purification by triplex affinity capture. 1992, Pubmed
Jacks, Tumor spectrum analysis in p53-mutant mice. 1994, Pubmed
King, Mitosis in transition. 1994, Pubmed
Knoblich, Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation. 1994, Pubmed
Kobayashi, On the synthesis and destruction of A- and B-type cyclins during oogenesis and meiotic maturation in Xenopus laevis. 1991, Pubmed , Xenbase
Kobayashi, Cyclins and their partners during Xenopus oocyte maturation. 1991, Pubmed , Xenbase
Koff, Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. 1992, Pubmed
Koff, Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta. 1993, Pubmed
Koff, Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. 1991, Pubmed , Xenbase
Lees, Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a temporally distinct manner. 1992, Pubmed
Leibovici, Characterization and developmental expression of Xenopus proliferating cell nuclear antigen (PCNA). 1990, Pubmed , Xenbase
Leno, The nuclear membrane prevents replication of human G2 nuclei but not G1 nuclei in Xenopus egg extract. 1992, Pubmed , Xenbase
Lew, Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. 1991, Pubmed
Lohka, Induction of nuclear envelope breakdown, chromosome condensation, and spindle formation in cell-free extracts. 1985, Pubmed , Xenbase
Lohka, Roles of cytosol and cytoplasmic particles in nuclear envelope assembly and sperm pronuclear formation in cell-free preparations from amphibian eggs. 1984, Pubmed , Xenbase
Mills, Replication occurs at discrete foci spaced throughout nuclei replicating in vitro. 1989, Pubmed , Xenbase
Minden, Direct cell lineage analysis in Drosophila melanogaster by time-lapse, three-dimensional optical microscopy of living embryos. 1989, Pubmed
Minshull, The A- and B-type cyclin associated cdc2 kinases in Xenopus turn on and off at different times in the cell cycle. 1990, Pubmed , Xenbase
Murray, Cyclin synthesis drives the early embryonic cell cycle. 1989, Pubmed , Xenbase
Nakayasu, Mapping replicational sites in the eucaryotic cell nucleus. 1989, Pubmed
Newmeyer, An N-ethylmaleimide-sensitive cytosolic factor necessary for nuclear protein import: requirement in signal-mediated binding to the nuclear pore. 1990, Pubmed , Xenbase
Newport, Disassembly of the nucleus in mitotic extracts: membrane vesicularization, lamin disassembly, and chromosome condensation are independent processes. 1987, Pubmed , Xenbase
Newport, Regulation of the cell cycle during early Xenopus development. 1984, Pubmed , Xenbase
Ohtsubo, Cyclin-dependent regulation of G1 in mammalian fibroblasts. 1993, Pubmed
Ohtsubo, Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. 1995, Pubmed
Pagano, Cyclin A is required at two points in the human cell cycle. 1992, Pubmed
Pagano, Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts. 1993, Pubmed
Pines, Isolation of a human cyclin cDNA: evidence for cyclin mRNA and protein regulation in the cell cycle and for interaction with p34cdc2. 1989, Pubmed
Pines, Cyclins and cyclin-dependent kinases: take your partners. 1993, Pubmed
Polyak, Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. 1994, Pubmed
Polyak, p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. 1994, Pubmed
Raska, Ultrastructural immunolocalization of cyclin/PCNA in synchronized 3T3 cells. 1989, Pubmed
Resnitzky, Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. 1994, Pubmed
Sawin, Mitotic spindle assembly by two different pathways in vitro. 1991, Pubmed , Xenbase
Sheehan, Steps in the assembly of replication-competent nuclei in a cell-free system from Xenopus eggs. 1988, Pubmed , Xenbase
Sherr, G1 phase progression: cycling on cue. 1994, Pubmed
Simanis, An immunoaffinity purification procedure for SV40 large T antigen. 1985, Pubmed
Sobczak-Thepot, Localization of cyclin A at the sites of cellular DNA replication. 1993, Pubmed
Solomon, Cyclin activation of p34cdc2. 1990, Pubmed , Xenbase
Toyoshima, p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. 1994, Pubmed
van den Heuvel, Distinct roles for cyclin-dependent kinases in cell cycle control. 1993, Pubmed
Waga, Reconstitution of complete SV40 DNA replication with purified replication factors. 1994, Pubmed
Waga, The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. 1994, Pubmed
Xiong, p21 is a universal inhibitor of cyclin kinases. 1993, Pubmed
Yan, An analysis of the regulation of DNA synthesis by cdk2, Cip1, and licensing factor. 1995, Pubmed , Xenbase
Zhang, p21-containing cyclin kinases exist in both active and inactive states. 1994, Pubmed
Zuber, Quantitation and subcellular localization of proliferating cell nuclear antigen (PCNA/cyclin) in oocytes and eggs of Xenopus laevis. 1989, Pubmed , Xenbase