Replication protein A 32 kDa subunit (RPA32)

Replication protein A 32 kDa subunit (RPA32, also known as RPA2) is a critical component of the heterotrimeric replication protein A (RPA) complex, which also includes the 70 kDa subunit (RPA1) and the 14 kDa subunit (RPA3). RPA32 contains an N-terminal flexible domain, a central oligonucleotide/oligosaccharide-binding (OB) fold DNA-binding domain (DBD D), and a C-terminal protein interaction domain. The central DNA-binding domain is essential for viability, supporting the structural and protein-protein interaction roles necessary for DNA replication, repair, and recombination. RPA32 can be phosphorylated, particularly at its N-terminal domain, which modulates protein interactions and the DNA damage response, linking it to cell cycle regulation and checkpoint control. Loss or dysfunction of RPA32, or its complex, leads to impaired DNA metabolism and cell viability, and its dysregulation is implicated in cancer and genomic instability disorders. RPA32 is not typically considered a classical drug target, but it is essential for cellular responses to genotoxic stress, and is under study as a potential therapeutic vulnerability in cancer, with phosphorylated RPA32 providing a readout for DNA checkpoint activation.

Other names

Replication protein A subunit 2RPA2RPA p32RFA2 (in yeast)replication protein A 32 kDa subunit (RPA32)replication factor A protein 2

Inhibition of single-stranded DNA binding by the RPA complex; Disruption of protein-protein interactions essential for DNA replication and repair; Modulation of phosphorylation status to alter DNA repair pathway choice.