Redox state of tumor suppressor p53 regulates its sequence-specific DNA binding in DNA-damaged cells by cysteine 277

Jiri Buzek, Leena Latonen, Sari Kurki, Karita Peltonen, Marikki Laiho

Research output: Contribution to journalArticle

Abstract

Using a bio-oligo pull-down DNA-binding assay we investigated the binding capacity of endogenous, DNA damage-induced p53 in human diploid fibroblasts to several p53-responsive elements (REs) present in p53-regulated genes. During the course of p53 accumulation, we observed a decrease in p53 binding to the GADD45 but not to the p21WAF1/CIP1 RE. Using mutated GADD45 sequences we show that this change is dependent on the presence of cytosines at position 3 in RE pentamers and on the p53 redox state. Site-directed mutagenesis experiments demonstrated that Cys277 (a residue directly contacting base 3 in a RE pentamer) is critical for differential regulation of GADD45 in DNA-damaged cells. These data represent a novel mechanism for differential affinity of p53 to distinct REs.

Original languageEnglish (US)
Pages (from-to)2340-2348
Number of pages9
JournalNucleic acids research
Volume30
Issue number11
StatePublished - Jun 1 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

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