Replication protein A 14 kDa subunit is a protein that in humans is encoded by the RPA3 gene. RPA is a single-stranded DNA-binding protein that is conserved in eukaryotes and plays essential roles in the metabolism of nucleic acids. Unlike helicase, RPA does not separate strands but binds and protects exposed single-stranded DNA to prevent secondary structure formation and degradation. RPA is usually considered to be the functional equivalent of bacterial single-stranded DNA-binding proteins (SSB), although it is much more complex structurally in eukaryotic cells.
RPA3 has been shown to interact with replication protein A1 and replication protein A2. Together, they form a heterotrimeric complex that contributes to the direct binding of single-stranded DNA during replication, homologous recombination, nucleoetide excision repair, and mismatch repair. RPA3 can directly contact ssDNA on the 3' side of a substrate, and this polarity is crucial for the positioning and stability of nucleases that are involved in excision repair