The multi‐replication protein A (RPA) system – a new perspective

Abstract

Replication protein A (RPA) complex has been shown, using both in vivo and in vitro approaches, to be required for most aspects of eukaryotic DNA metabolism: replication, repair, telomere maintenance and homologous recombination. Here, we review recent data concerning the function and biological importance of the multi‐RPA complex. There are distinct complexes of RPA found in the biological kingdoms, although for a long time only one type of RPA complex was believed to be present in eukaryotes. Each complex probably serves a different role. In higher plants, three distinct large and medium subunits are present, but only one species of the smallest subunit. Each of these protein subunits forms stable complexes with their respective partners. They are paralogs as complex. Humans possess two paralogs and one analog of RPA. The multi‐RPA system can be regarded as universal in eukaryotes. Among eukaryotic kingdoms, paralogs, orthologs, analogs and heterologs of many DNA synthesis‐related factors, including RPA, are ubiquitous. Convergent evolution seems to be ubiquitous in these processes. Using recent findings, we review the composition and biological functions of RPA complexes.

Telomerase Is Essential to Alleviate Pif1-Induced Replication Stress at Telomeres

“…Rfa1 and Mre11 foci form upon strong overexpression of PIF1: Replication protein A (RPA), which consists of the subunits Rfa1, Rfa2, and Rfa3, binds single-stranded DNA (ssDNA) and is important for most aspects of eukaryotic DNA metabolism (Sakaguchi et al 2009). RPA-coated ssDNA is a key structure for the activation of the DNA damage checkpoint response (Zou and Elledge 2003).…”

The Recombinases DMC1 and RAD51 Are Functionally and Spatially Separated during Meiosis in Arabidopsis

“…Several additional factors may influence RAD51 and DMC1 filament assembly. RPA, for instance, modulates meiotic recombination in yeast (Bartrand et al, 2006;Liaw et al, 2011), and several members for each of the three subunits, one of which is implicated in meiotic DSB repair, are encoded in the genome of Arabidopsis (Shultz et al, 2007;Osman et al, 2009;Sakaguchi (A) Nuclear spreads of PMCs during metaphase I displaying five bivalents in atr rad51 and 10 univalents in atr rad51 asy1 triple mutants. (B) Quantification of meiocytes with univalents, bivalents, or both (irrespective of DNA fragmentation).…”

MEIOTIC F-BOX Is Essential for Male Meiotic DNA Double-Strand Break Repair in Rice

“…The DSB ends are resected by the meiotic recombination 11-radiation sensitive50 (RAD50)-Nijmegen breakage syndrome 1/X-ray-sensitive2 complex, together with completion of meiosis I (COM1)/sporulation in the absence of SPO11 (SAE2) to produce a long 39-OH single-stranded DNA molecule. The nascent single-stranded DNA is bound by replication protein A (RPA) (Sakaguchi et al, 2009;Li et al, 2013;Aklilu et al, 2014). RAD51 and disrupted meiotic cDNA (DMC1) are then recruited to promote single-strand invasion of homologous regions of DNA.…”