A role for p53 in base excision repair

Wild-type p53 protein can markedly stimulate base excision repair (BER) in vitro, either reconstituted with purified components or in extracts of cell s. In contrast, p53 with missense mutations either at hotspots 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 inte ract directly both with the AP endonuclease (APE) and with DNA polymerase b eta (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 c ell extracts closely parallels their levels of endogenous p53, and that BER activity is much reduced in cell extracts immunodepleted of p53. These dat a suggest a novel role for p53 in DNA repair, which could contribute to its function as a key tumor suppressor.