RPA involvement in the damage-recognition and incision steps of nucleotide excision repair

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Abstract
HUMAN replication protein (RPA) functions in DNA replication1-4, homologous recombination5 and nucleotide excision repair6. This multisubunit single-stranded DNA-binding protein1,2 may be required to make unique protein-protein contacts because heterol-ogous single-stranded binding proteins cannot substitute for RPA in these diverse DNA transactions5-7. We report here that, by using affinity chromatography and immunoprecipitation, we found that human RPA bound specifically and directly to two excision repair proteins, the xeroderma pigmentosum damage-recognition protein XPA (refs 8, 9) and the endonuclease XPG (refs 10-13). Although it had been suggested that RPA might function before the DNA synthesis repair stage14,15, our finding that a complex of RPA and XPA showed a striking cooperativity in binding to DNA lesions indicates that RPA may function at the very earliest stage of excision repair. In addition, by binding XPG, RPA may target this endonuclease to damaged DNA.