RPA INVOLVEMENT IN THE DAMAGE-RECOGNITION AND INCISION STEPS OF NUCLEOTIDE EXCISION-REPAIR

HUMAN replication protein (RPA) functions in DNA replication(1-4), hom ologous recombination(5) and nucleotide excision repair(6). This multi subunit single-stranded DNA-binding protein(1,2) may be required to ma ke unique protein-protein contacts because heterologous single-strande d binding proteins cannot substitute for RPA in these diverse DNA tran sactions(5-7). We report here that, by using affinity chromatography a nd immunoprecipitation, we found that human RPA bound specifically and directly to two excision repair proteins, the xeroderma pigmentosum d amage-recognition protein XPA (refs 8, 9) and the endonuclease XPG (re fs 10-13). Although it had been suggested that RPA might function befo re the DNA synthesis repair stage(14.15), our finding that a complex o f RPA and XPA showed a striking cooperativity in binding to DNA lesion s indicates that RPA may function at the very earliest stage of excisi on repair. In addition, by binding XPG, RPA may target this endonuclea se to damaged DNA.