Replication protein A 70 kDa subunit N-terminal domain (RPA70N)

Replication protein A 70 kDa subunit N-terminal domain (RPA70N) is a critical protein-interaction module within the largest subunit (RPA1) of the heterotrimeric Replication Protein A (RPA) complex (UniProt: P27694) [1]. RPA is the primary eukaryotic single-stranded DNA (ssDNA) binding protein, essential for DNA replication, recombination, and repair. The RPA70N domain specifically utilizes an oligonucleotide/oligosaccharide-binding (OB) fold to act as a scaffold, recruiting various DNA damage response (DDR) proteins such as ATRIP, p53, and RAD9 to sites of DNA damage [2]. Because of its central role in coordinating repair pathways, RPA70N has emerged as a significant therapeutic target in oncology. Small molecule inhibitors, such as TDRL-505, target the RPA70N domain to block these protein-protein interactions, thereby sensitizing cancer cells to chemotherapy and radiotherapy by preventing effective DNA repair [3]. Research indicates that disrupting RPA70N function can lead to increased genomic instability and apoptosis in tumor cells, particularly in those with existing DDR deficiencies [2].

Other names

RPA1 N-terminal domainReplication protein A1 N-terminal domainRPA70-NOB-A domain of RPA1RPA70 N-terminal OB-fold

Inhibition of protein-protein interactions (PPI) between the RPA70N domain and DNA damage response proteins (e.g., ATRIP, p53, RAD9) to disrupt DNA repair signaling and sensitize cells to DNA-damaging agents [2, 3].