Subunit
name Gene | Gene Chromosomal
locus | |
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Replication protein A (RPA) is the major protein that binds to single-stranded DNA (ssDNA) in eukaryotic cells. In vitro, RPA shows a much higher affinity for ssDNA than RNA or double-stranded DNA.
During DNA replication, RPA prevents single-stranded DNA (ssDNA) from winding back on itself or from forming secondary structures. This keeps DNA unwound for the polymerase to replicate it. RPA also binds to ssDNA during the initial phase of homologous recombination, an important process in DNA repair and prophase I of meiosis.
Hypersensitivity to DNA damaging agents can be caused by mutations in the RPA gene. Like its role in DNA replication, this keeps ssDNA from binding to itself (self-complementizing) so that the resulting nucleoprotein filament can then be bound by Rad51 and its cofactors.
RPA also binds to DNA during the nucleotide excision repair process. This binding stabilizes the repair complex during the repair process. A bacterial homolog is called single-strand binding protein (SSB).
Structure
RPA is a heterotrimer, composed of the subunits RPA1 (70kDa subunit), RPA2 (32kDa subunit) and RPA3 (14kDa subunit). The three RPA subunits contain four OB-folds (oligonucleotide/oligosaccharide binding) that bind RPA to single-stranded DNA. RPA shares many features with the CST Complex heterotrimer, although RPA has a more uniform 1:1:1 stoichiometry.