Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA

The single-stranded-DNA-binding proteins (SSBs) are essential for DNA function in prokaryotic and eukaryotic cells, mitochondria, phage and viruses [1,2]. The structures of four SSBs have been solved [3-7], but the molecular details of the interactions of SSBs with DNA remain speculative. We report here the crystal structure of 2.4 Angstrom resolution of the single-stranded-DNA-binding domain of human replication protein A (RPA) bound to DNA. Replication protein A is a heterotrimeric SSB that is highly conserved in eukaryotes. The largest subunit, RPA70, binds to single-stranded (ss) DNA [8,9] and mediates interactions with many cellular and viral proteins [10]. The DNA-binding domain, which cellular and middle of RPA70, comprises two structurally homologous subdomains oriented in tandem. The ssDNA lies in a channel that extends from one subdomain to the other. The structure of each RPA70 subdomain is similar to those of the bacteriophage SSBs, indicating that the mechanism of ssDNA-binding is conserved.