Structural and functional involvement of p53 in BER in vitro and in vivo

p53 is involved in several DNA repair pathways. Some of these require the s pecific transactivation of p53-dependent genes and others involve direct in teractions between the p53 protein and DNA repair associated proteins. Prev iously, we have shown that p53 acts directly in Base Excision Repair (BER) when assayed under in vitro conditions. Our present data indicate that this involvement is independent of the transcriptional activity of the p53 mole cule. We found that under both in vitro and in vivo conditions, a p53 trans activation-deficient molecule, p53-22-23,was more efficient in BER activity than was wild type p53. However, mutations in the core domain or C-termina l alterations strongly reduced p53-mediated BER activity, These results are consistent with the hypothesis that the involvement of p53 in BER activity , a housekeeping DNA repair pathway, is a prompt and immediate one that doe s not involve the activation of D53 transactivation-dependent mechanisms, b ut rather concerns with the p53 protein itself. In an endogenous DNA damage status p53 is active in BER pathways as a protein and not as a transcripti on factor.