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PMID: 12034830 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Interactions between p53, hMSH2-hMSH6 and HMG I(Y) on Holliday junctions and bulged bases.

Nucleic acids research ·Vol. 30 ·No. 11 ·2002-06-01 ·Pages 2427-34

Subramanian D, Griffith JD

Abstract

The ability of the tumor suppressor protein, p53, to recognize certain types of DNA lesions may represent one of the mechanisms by which this protein modulates cellular response to DNA damage. p53 DNA binding properties are regulated by several factors, such as post-translational modifications including phosphorylation and acetylation, regulation by its own C-terminal domain and interactions with other cellular proteins. Substrates resembling Holliday junctions and extra base bulges were used to study the effect of three nuclear proteins, HMG-1, HMG I(Y) and hMSH2-hMSH6, on the lesion binding properties of p53. Gel retardation assays revealed that the three proteins had varying effects on p53 binding to these substrates. HMG-1 did not influence p53 binding to Holliday junctions or 3-cytosine bulges. HMG I(Y) rapidly dissociated p53 complexes with Holliday junctions but not 3-cytosine bulges. Finally, the mismatch repair protein complex, hMSH2-hMSH6, enhanced p53 binding to both substrates by 3-4-fold. Together, these results demonstrate that p53 DNA binding activity is highly influenced by the presence of other proteins, some having a dominant effect while others have a negative effect.

MeSH Terms
Animals Base Pair Mismatch Cattle Cytosine/chemistry,metabolism DNA/chemistry,genetics,metabolism DNA Repair DNA-Binding Proteins/metabolism HMGA1a Protein/metabolism Humans MutS Homolog 2 Protein Nucleic Acid Conformation Protein Binding Proto-Oncogene Proteins/metabolism Recombination, Genetic Tumor Suppressor Protein p53/metabolism
Chemicals
DNA-Binding Proteins G-T mismatch-binding protein Proto-Oncogene Proteins Tumor Suppressor Protein p53 HMGA1a Protein Cytosine DNA MSH2 protein, human MutS Homolog 2 Protein
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Subramanian Deepa
Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, CB 7295 Mason Farm Road, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Griffith Jack D
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
Published
2002-06-01
Pages
2427-34
Language
English
Region
England
NLM ID
0411011
PMCID
PMC117204
Subset
IM
Grants
NIGMS NIH HHS · R01 GM031819 · United States
NCI NIH HHS · CA70343 · United States
NIGMS NIH HHS · GM31819 · United States
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