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PMID: 9207066 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Interaction between replication protein A and p53 is disrupted after UV damage in a DNA repair-dependent manner.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 14 ·1997-07-08 ·Pages 7186-91

Abramova NA, Russell J, Botchan M, Li R

Abstract

Replication protein A (RPA) is required for both DNA replication and nucleotide excision repair. Previous studies have shown that RPA interacts with the tumor suppressor p53. Herein, we have mapped a 20-amino acid region in the N-terminal part of p53 that is essential for its binding to RPA. This region is distinct from the minimal activation domain of p53 previously identified. We also demonstrate that UV radiation of cells greatly reduces the ability of RPA to bind to p53. Interestingly, damage-induced hyperphosphorylated RPA does not associate with p53. Furthermore, down-regulation of the RPA/p53 interaction is dependent upon the capability of cells to perform global genome repair. On the basis of these data, we propose that RPA may participate in the coordination of DNA repair with the p53-dependent checkpoint control by sensing UV damage and releasing p53 to activate its downstream targets.

MeSH Terms
Animals Binding Sites Cell Line DNA Repair DNA-Binding Proteins/metabolism Mutation Peptide Mapping Protein Binding Replication Protein A Tumor Suppressor Protein p53/chemistry,genetics,metabolism
Chemicals
DNA-Binding Proteins Replication Protein A Tumor Suppressor Protein p53
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Abramova N A
Department of Biochemistry, Health Sciences Center, University of Virginia, Charlottesville, VA 22908, USA.
Russell J
Botchan M
Li R
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.14.7186
Published
1997-07-08
Pages
7186-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23787
Subset
IM
Grants
NIEHS NIH HHS · ES-01896 · United States
NCI NIH HHS · CA-30490 · United States
NIEHS NIH HHS · P30 ES001896 · United States
NCI NIH HHS · R37 CA030490 · United States
NCI NIH HHS · R01 CA030490 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.14.7186 PMC Full Text View journal details
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