Direct involvement of p53 in the base excision repair pathway of the DNA repair machinery

The p53 turner suppressor that plays a central role in the cellular respons e to genotoxic stress was suggested to be associated with the DNA repair ma chinery which mostly involves nucleotide excision repair (NER). In the pres ent study we show for the first time that p53 is also directly involved in base excision repair (BER), These experiments were performed with p53 tempe rature-sensitive (ts) mutants that were previously studied in in vivo exper imental models. We report here that p53 ts mutants can also acquire wild-ty pe activity under in vitro conditions. Using ts mutants of murine and human origin, it was observed that cell extracts overexpressing p53 exhibited an augmented BER activity measured in an in vitro assay. Depletion of p53 fro m the nuclear extracts abolished this enhanced activity. Together, this sug gests that p53 is involved in more than one DNA repair pathway, (C) 1999 Fe deration of European Biochemical Societies.