title: A role for p53 in base excision repair.
abstract: Wild-type p53 protein can markedly stimulate base excision repair (BER) in vitro, either reconstituted with purified components or in extracts of cells. In contrast, p53 with missense mutations either at hot-spots in the core domain or within the N-terminal transactivation domain is defective in this function. Stimulation of BER by p53 is correlated with its ability to interact directly both with the AP endonuclease (APE) and with DNA polymerase beta (pol beta). Furthermore, p53 stabilizes the interaction between DNA pol beta and abasic DNA. Evidence that this function of p53 is physiologically relevant is supported by the facts that BER activity in human and murine cell extracts closely parallels their levels of endogenous p53, and that BER activity is much reduced in cell extracts immunodepleted of p53. These data suggest a novel role for p53 in DNA repair, which could contribute to its function as a key tumor suppressor.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10025, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: J
authors.initials: J
authors.lastname: Ahn
authors.forename: S H
authors.initials: SH
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Prives
mesh_terms: D001483:Base Sequence; D019951:DNA Polymerase beta / Q000378:metabolism; D017931:DNA Primers; D004260:DNA Repair / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; D016159:Tumor Suppressor Protein p53; D019951:DNA Polymerase beta