RFA1, RFA2, and RFA3 encode the three subunits of the heterotrimeric complex Replication protein A (RPA). RPA is a highly conserved single-stranded DNA (ssDNA) binding protein that removes secondary structure from ssDNA. RPA plays a key role in DNA metabolic pathways that have a ssDNA intermediate such as replication, recombination, transcription, checkpoints, telomere maintenance, and DNA repair (reviewed in 8 and 9). Some specific instances of RPA function in yeast include loading the telomerase component Est1p onto telomeres (10), enabling the efficient assembly of the Rad51p presynaptic filament (11, 12), and providing specificity of Rad17p/Mec3p/Ddc1p loading at 5'-junctions (13).

RPA binds ssDNA with high affinity and has no sequence specificity but does preferentially bind to pyrimidines over purines (6, 14). RPA interaction with DNA is mediated by binding domains in Rfa1p and Rfa2p (15). In response to DNA damage, Rfa1p and Rfa2p are phosphorylated by overlapping mechanisms that involve the kinases Mec1p and Tel1p (16, 17, 18). These same kinases also mediate Rfa2p phosphorylation during the normal cell cycle and during meiosis (16, 19).

All three RFA subunits are essential for viability in yeast, but reduction of function mutations in RPA result in various defects such as sensitivity to DNA damaging agents, altered mitotic and meiotic recombination, failure in mating type switching, severe telomere shortening, and chromosomal instability (10, 12 and reviewed in 9, 20). Gross chromosomal rearrangements found in rfa1 mutants are similar to those seen in some human cancers, and corresponding mutations in mice lead to tumor development (21 and references therein).

Last updated: 2007-08-09