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PMID: 7642695 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Early events in DNA replication require cyclin E and are blocked by p21CIP1.

The Journal of cell biology ·Vol. 130 ·No. 4 ·1995-08-00 ·Pages 755-69

Jackson PK, Chevalier S, Philippe M, Kirschner MW

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.

MeSH Terms
Amino Acid Sequence Animals Aphidicolin/pharmacology CDC2-CDC28 Kinases Cell Cycle Proteins Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinases/antagonists & inhibitors,metabolism Cyclins/immunology,metabolism DNA Replication/drug effects,physiology DNA, Single-Stranded/metabolism Female Fungal Proteins/immunology,metabolism Male Mitosis/physiology Molecular Sequence Data Ovum Precipitin Tests Proliferating Cell Nuclear Antigen/metabolism Protein Binding Protein Serine-Threonine Kinases/antagonists & inhibitors,metabolism Schizosaccharomyces pombe Proteins Spermatozoa Xenopus Xenopus Proteins
Chemicals
Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p21 Cyclins DNA, Single-Stranded Fungal Proteins Proliferating Cell Nuclear Antigen Schizosaccharomyces pombe Proteins Suc1 protein, S pombe Xenopus Proteins Aphidicolin Protein Serine-Threonine Kinases CDC2-CDC28 Kinases Cdk2 protein, Xenopus Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jackson P K
Harvard Medical School, Department of Cell Biology, Boston, Massachusetts 02115, USA.
Chevalier S
Philippe M
Kirschner M W
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.130.4.755
Published
1995-08-00
Pages
755-69
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2199964
Subset
IM
Grants
NIGMS NIH HHS · GM39023-05 · United States
External Links
PubMed source DOI: 10.1083/jcb.130.4.755 PMC Full Text View journal details
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