Document Detail


tumor suppressor p53 binds with high affinity to CTG.CAG trinucleotide repeats and induces topological alterations in mismatched duplexes.
MedLine Citation:
PMID:  16230356     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
DNA binding is central to the ability of p53 to function as a tumor suppressor. In line with the remarkable functional versatility of p53, which can act on DNA as a transcription, repair, recombination, replication, and chromatin accessibility factor, the modes of p53 interaction with DNA are also versatile. One feature common to all modes of p53-DNA interaction is the extraordinary sensitivity of p53 to the topology of its target DNA. Whereas the strong impact of DNA topology has been demonstrated for p53 binding to sequence-specific sites or to DNA lesions, the possibility that DNA structure-dependent recognition may underlie p53 interaction with other types of DNA has not been addressed until now. We demonstrate for the first time that conformationally flexible CTG.CAG trinucleotide repeats comprise a novel class of p53-binding sites targeted by p53 in a DNA structure-dependent mode in vitro and in vivo. Our major finding is that p53 binds to CTG.CAG tracts by different modes depending on the conformation of DNA. Although p53 binds preferentially to hairpins formed by either CTG or CAG strands, it can also bind to linear forms of CTG.CAG tracts such as canonic B DNA or mismatched duplex. Intriguingly, by binding to a mismatched duplex p53 can induce further topological alterations in DNA, indicating that p53 may act as a DNA topology-modulating factor.
Authors:
Korden Walter; Gabriele Warnecke; Richard Bowater; Wolfgang Deppert; Ella Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-26     Completed Date:  2006-02-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  42497-507     Citation Subset:  IM    
Affiliation:
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Martinistrasse 52, D-20251, Hamburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Base Pair Mismatch*
Binding Sites
Cell Line, Tumor
Chromatin / chemistry
Chromatin Immunoprecipitation
Cloning, Molecular
DNA / chemistry*
DNA, Single-Stranded / genetics
Deoxyribonucleases / chemistry
Genes, Reporter
Genes, p53*
Humans
Luciferases / metabolism
Molecular Conformation
Nucleic Acid Conformation
Oligonucleotides / chemistry
Protein Binding
Protein Conformation
Transfection
Trinucleotide Repeats*
Tumor Suppressor Protein p53 / chemistry*,  genetics*
Chemical
Reg. No./Substance:
0/Chromatin; 0/DNA, Single-Stranded; 0/Oligonucleotides; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 9007-49-2/DNA; EC 1.13.12.-/Luciferases; EC 3.1.-/Deoxyribonucleases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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