HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 52, 42497-42507, December 30, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/52/42497    most recent M507038200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walter, K. Articles by Kim, E. Search for Related Content PubMed PubMed Citation Articles by Walter, K. Articles by Kim, E. Social Bookmarking                      What's this?

Tumor Suppressor p53 Binds with High Affinity to CTG·CAG Trinucleotide Repeats and Induces Topological Alterations in Mismatched Duplexes^*

Korden Walter, Gabriele Warnecke, Richard Bowater, Wolfgang Deppert, and Ella Kim¶1

From the Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Martinistrasse 52, D-20251, Hamburg, Germany, the School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, United Kingdom, and the ^¶Neuro-Oncology Group, Department of Neurosurgery, University of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany

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.

Received for publication, June 28, 2005 , and in revised form, September 19, 2005.

^* This work was supported by Deutsche Forschungsgemeinschaft Grant De 212/19-4,-5, by the Fonds der Chemischen Industrie, and by European Community FP6 funding. The Heinrich-Pette-Institut is financially supported by the Freie und Hansestadt Hamburg and the Bundesministerium für Gesundheit und Soziales. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S3.

¹ To whom correspondence should be addressed: Neuro-Oncology Group, Dept. of Neurosurgery, University of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. Tel.: 49-451500-6722; Fax: 49-451500-6191; E-mail: ella.kim{at}neurochirurgie.uni-luebeck.de.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. J. Krieg, E. M. Hammond, and A. J. Giaccia Functional Analysis of p53 Binding under Differential Stresses. Mol. Cell. Biol., October 1, 2006; 26(19): 7030 - 7045. [Abstract] [Full Text] [PDF]