Replication protein A (RPA)

Replication protein A (RPA) is the major eukaryotic single-stranded DNA-binding protein, essential for stabilizing exposed single-stranded DNA during critical cellular processes such as DNA replication, repair, and recombination[1][2][4][5][8]. Structurally, RPA is a heterotrimeric complex, in humans comprising three subunits: RPA1 (RPA70), RPA2 (RPA32), and RPA3 (RPA14)[1][2][6]. These subunits assemble to form multiple oligonucleotide/oligosaccharide binding (OB) folds responsible for high-affinity binding to ssDNA and for mediating protein-protein interactions with DNA repair, checkpoint, and replication factors[1][2][8]. RPA is required for nearly all nuclear processes involving ssDNA, serving both as a DNA stabilizer and as a versatile interaction platform. Aberrations in RPA function or regulation are implicated in cancer and other diseases involving genome instability, making it a potential therapeutic target, especially in oncology[5].

Other names

Replication factor ARPA complexRF-ARfa (yeast; subunit names: Rfa1, Rfa2, Rfa3)

Inhibitors typically act by blocking RPA's binding to single-stranded DNA, thereby preventing essential DNA replication and repair processes in cancer cells[5].