The single-stranded-DNA-binding proteins (SSBs) are essential for DNA function in prokaryotic and eukaryotic cells, mitochondria, phages and viruses. Replication protein A (RPA), a highly conserved eukaryotic protein, is a heterotrimeric SSB. RPA plays an important role in DNA replication, recombination and repair. The binding of human RPA (hRPA) to DNA involves molecular polarity in which initial hRPA binding occurs on the 5' side of an ssDNA substrate and then extends in the 3' direction to create a stably bound hRPA. RPA is a major damage-recognition protein involved in the early stages of nucleotide excision repair. It can also play a role in telomere maintenance. The RPA 70 kDa subunit binds to ssDNA and mediates interactions with many cellular and viral proteins. The DNA binding domain lies in the middle of RPA 70 kDa subunit and comprises two structurally homologous subdomains oriented in tandem. RPA contains a conserved four cysteine-type zinc-finger motif, which mediates the transition of RPA-ssDNA interaction to a stable RPA-ssDNA complex in a redox-dependent manner.