title: The C-terminal domain of p53 recognizes DNA damaged by ionizing radiation.
abstract: p53 accumulates after DNA damage and arrests cellular growth. These findings suggest a possible role for p53 in the cellular response to DNA damage. We have previously shown that the C terminus of p53 binds DNA nonspecifically and assembles stable tetramers. In this study, we have utilized purified segments of human and murine p53s to determine which p53 domains may participate in a DNA damage response pathway. We find that the C-terminal 75 amino acids of human or murine p53 are necessary and sufficient for the DNA annealing and strand-transfer activities of p53. In addition, both full-length wild-type p53 and the C-terminal 75 amino acids display an increased binding affinity for DNA damaged by restriction digestion, DNase I treatment, or ionizing radiation. In contrast, the central site-specific DNA-binding domain together with the tetramerization domain does not have these activities. We propose that interactions of the C terminus of p53 with damaged DNA may play a role in the activation of p53 in response to DNA damage.
authors.affiliation: Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook 11794, USA.
authors.forename: M
authors.initials: M
authors.lastname: Reed
authors.forename: B
authors.initials: B
authors.lastname: Woelker
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M E
authors.initials: ME
authors.lastname: Anderson
authors.forename: P
authors.initials: P
authors.lastname: Tegtmeyer
mesh_terms: D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011839:Radiation, Ionizing; D011994:Recombinant Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA