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: |
|
Communities: |
CSHL labs > Hannon lab CSHL labs > Stillman lab |
Highlight: |
Stillman, Bruce W. |
Depositing User: |
Matt Covey
|
Date: |
1994 |
Date Deposited: |
09 Jan 2013 17:38 |
Last Modified: |
20 Jun 2017 19:54 |
Related URLs: |
|
URI: |
http://repository.cshl.edu/id/eprint/26488 |
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