Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair

Li, R., Waga, S., Hannon, G. J., Beach, D., Stillman, B. (1994) Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature, 371 (6497). pp. 534-537. ISSN 00280836 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/7935768
DOI: 10.1038/371534a0

Abstract

In mammalian cells, DNA damage increases the levels of the nuclear tumour-suppressor p53, resulting in elevated synthesis of p21, an inhibitor of cyclin-dependent kinases (CDK). p21 may also directly block DNA replication by inhibiting the proliferating cell nuclear antigen (PCNA), an essential DNA replication protein. However, PCNA is also required for nucleotide-excision repair of DNA, an intrinsic part of the cellular response to ultraviolet irradiation. Using an in vitro system, we now show that p21 does not block PCNA-dependent nucleotide-excision repair, in contrast to its inhibition of simian virus 40 DNA replication. Furthermore, the short gap-filling DNA synthesis by PCNA dependent DNA polymerases δ and ε is less sensitive to inhibition by p21 than is long primer-extension synthesis. The ability of p21 to inhibit the role of PCNA in DNA replication but not in DNA repair rationalizes in vivo data showing that genetic damage leads to inactivation of chromosomal replication while allowing damage responsive repair.

Item Type: Paper
Uncontrolled Keywords: cycline protein p21 article carcinoma cell colon carcinoma dna replication excision repair human human cell priority journal tumor suppressor gene p53 Cell Line Cyclins DNA Repair DNA, Viral DNA-Directed DNA Polymerase Proliferating Cell Nuclear Antigen Protein Kinases Simian virus 40 Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Tumor Cells, Cultured Mammalia 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
CSHL Authors:
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:
URI: http://repository.cshl.edu/id/eprint/26489

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