Replication protein A 70 kDa subunit (RPA1) (RPA70N)

Replication protein A (RPA) is a heterotrimeric complex consisting of RPA70, RPA32, and RPA14 subunits, serving as the primary eukaryotic single-stranded DNA (ssDNA) binding protein (UniProt: P27694). The N-terminal domain of the 70 kDa subunit (RPA70N) is a critical protein-protein interaction hub that recruits various DNA damage response (DDR) and repair proteins, such as ATRIP, p53, RAD9, and MRE11, to sites of DNA damage (PMID: 23303794). In many cancers, RPA is overexpressed to manage high levels of replication stress and maintain genomic integrity, making it a viable therapeutic target (PMID: 26851211). Small molecule inhibitors targeting the RPA70N domain work by blocking the binding of these essential partner proteins, thereby disrupting DNA repair pathways and sensitizing tumors to DNA-damaging therapies (PMID: 24403073). This strategy is particularly effective in cancers with existing DNA repair deficiencies, where RPA inhibition can induce synthetic lethality. Current research focuses on optimizing these inhibitors to enhance potency and selectivity while minimizing impact on normal cellular replication.

Other names

RPA1RF-A protein 1Replication factor A protein 1Single-stranded DNA-binding proteinP70RPA70N

Inhibition of protein-protein interactions between the RPA70 N-terminal domain and DNA damage response proteins