Single-stranded DNA-binding protein (SSB) (SSB)

Single-stranded DNA-binding protein (SSB), known as Replication Protein A (RPA) in eukaryotes, is a critical factor in nearly all aspects of DNA metabolism. Its primary role is to bind and stabilize single-stranded DNA (ssDNA) intermediates that form during replication, repair, and recombination, preventing them from forming secondary structures or being degraded by nucleases [1][2]. In humans, the RPA heterotrimer (comprising RPA1, RPA2, and RPA3) coordinates the recruitment of various enzymes to sites of DNA damage, acting as a central hub for the DNA damage response (DDR) [3]. Because cancer cells often exhibit high levels of replicative stress and depend on robust DDR pathways for survival, RPA has emerged as a promising therapeutic target for sensitizing tumors to DNA-damaging agents [4]. Small molecule inhibitors, such as TDRL-505, are designed to block the interaction between RPA and ssDNA or its protein partners to induce synthetic lethality in repair-deficient cancers [5]. Additionally, bacterial SSB proteins are structurally distinct from human counterparts, making them viable targets for the development of novel antimicrobial agents [6].

Other names

Replication protein ARPASingle-stranded DNA-binding protein 1SSBP1Mitochondrial single-stranded DNA-binding proteinmtSSBReplication factor ARFA

Inhibition of single-stranded DNA binding and disruption of protein-protein interactions within the DNA damage response machinery.