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 a 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 C-terminus of RPA 32 can specfically intereact with the DNA repair enzyme UNG2 and repair factors XPA and Rad52, each of which functions in a different repair pathway. In addition, RPA 32 binds specifically to the SH2 domain of Stat3 in vivo, and overexpression of RPA 32 corresponds to the augmented growth factor-stimulated tyrosine phosphorylation and transcription activities of Stat3.