The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA

Waga, S., Hannon, G. J., Beach, D., Stillman, B. (1994) The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature, 369 (6481). pp. 574-578. ISSN 00280836 (ISSN)

Abstract

The p53 tumour-suppressor protein controls the expression of a gene encoding the p21 cyclin-dependent protein kinase (CDK) regulator. Levels of p21 protein are increased in senescent cells and p21 overexpression blocks the growth of tumour cells. In normal human cells, but not in many tumour cells, p21 exists in a quaternary complex with a cyclin, a CDK, and the proliferating-cell nuclear antigen (PCNA). p21 controls CDK activity, thereby affecting cell-cycle control, whereas PCNA functions in both DNA replication and repair. Here we use simian virus 40 DNA replication in vitro to show that p21 directly inhibits PCNA-dependent DNA replication in the absence of a cyclin/CDK. Furthermore, p21 blocks the ability of PCNA to activate DNA polymerase δ, the principal replicative DNA polymerase. This regulation results from a direct interaction between p21 and PCNA. Thus, during p53-mediated suppression of cell proliferation, p21 and PCNA may be important for coordinating cell-cycle progression, DNA replication and repair of damaged DNA.

Item Type:	Paper
Uncontrolled Keywords:	cycline protein kinase inhibitor protein p21 article cell cycle dna repair dna replication priority journal protein interaction Cell Division Cell Line Cyclins DNA Polymerase III DNA Topoisomerases, Type I DNA, Viral DNA-Directed DNA Polymerase Histidine Human Nuclear Proteins Proliferating Cell Nuclear Antigen Protein Kinases Recombinant Proteins Simian virus 40 Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Simiae Simian virus
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:	Beach, David H. Hannon, Gregory J. Stillman, Bruce W.
Communities:	CSHL labs > Hannon lab CSHL labs > Stillman lab
Highlight:	Stillman, Bruce W.
Depositing User:	Matt Covey
Date Deposited:	09 Jan 2013 17:38
Last Modified:	20 Jun 2017 19:54
Related URLs:	Publisher
URI:	http://repository.cshl.edu/id/eprint/26488

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