INTERACTION BETWEEN REPLICATION PROTEIN-A AND P53 IS DISRUPTED AFTER UV DAMAGE IN A DNA REPAIR-DEPENDENT MANNER

Replication protein A (RPA) is required for both DNA replication and n ucleotide excision repair. Previous studies have shown that RPA intera cts with the tumor suppresser p53. Herein, we have mapped a 20-amino a cid region in the N-terminal part of p53 that is essential for its bin ding to RPA. This region is distinct from the minimal activation domai n of p53 previously identified. We also demonstrate that UV radiation of cells greatly reduces the ability of RPA to bind to p53. Interestin gly, damage-induced hyperphosphorylated RPA does not associate with p5 3. Furthermore, downregulation of the RPA/p53 interaction is dependent upon the capability of cells to perform global genome repair. On the basis of these data, we propose that RPA may participate in the coordi nation of DNA repair with the p53-dependent checkpoint control by sens ing UV damage and releasing p53 to activate its downstream targets.