RPA homologs and ssDNA processing during meiotic recombination

Abstract

Meiotic homologous recombination is a specialized process that involves homologous chromosome pairing and strand exchange to guarantee proper chromosome segregation and genetic diversity. The formation and repair of DNA double-strand breaks (DSBs) during meiotic recombination differs from those during mitotic recombination in that the homologous chromosome rather than the sister chromatid is the preferred repair template. The processing of single-stranded DNA (ssDNA) formed on intermediate recombination structures is central to driving the specific outcomes of DSB repair during meiosis. Replication protein A (RPA) is the main ssDNA-binding protein complex involved in DNA metabolism. However, the existence of RPA orthologs in plants and the recent discovery of meiosis specific with OB domains (MEIOB), a widely conserved meiosis-specific RPA1 paralog, strongly suggest that multiple RPA complexes evolved and specialized to subdivide their roles during DNA metabolism. Here we review ssDNA formation and maturation during mitotic and meiotic recombination underlying the meiotic specific features. We describe and discuss the existence and properties of MEIOB and multiple RPA subunits in plants and highlight how they can provide meiosis-specific fates to ssDNA processing during homologous recombination. Understanding the functions of these RPA homologs and how they interact with the canonical RPA subunits is of major interest in the fields of meiosis and DNA repair.Electronic supplementary materialThe online version of this article (doi:10.1007/s00412-015-0552-7) contains supplementary material, which is available to authorized users.

Age-Dependent Alterations in Meiotic Recombination Cause Chromosome Segregation Errors in Spermatocytes

“…We found that spermatocytes from juveniles had the same number of DMC1 foci as adults, indicating that early recombination intermediates and likely DSB formation are similar at both stages (Figure 1A). Early recombination intermediates are also marked by RPA2, which facilitates recombination (Ribeiro et al, 2016). While RPA2 foci peak during zygonema, half of early intermediates remain marked in pachynema, when RPA2 is thought to mark stable interhomolog interactions.…”

Repair of Meiotic DNA Breaks and Homolog Pairing in Mouse Meiosis Requires a Minichromosome Maintenance (MCM) Paralog

“…Despite the synapsis defects, RPA2 decorated axial elements of zygotene-like mutant spermatocyte chromosomes in a pattern indistinguishable from wild-type, suggesting that meiotic DSBs were normally formed and resected in the absence of MCMDC2 ( Figure 4A). Approximately contemporaneous to RPA loading (Ribeiro et al 2016), the resected ends of DSBs are also bound by recA homologs RAD51 and DMC1, forming cytologically visible foci along SC cores (250 per leptotene nucleus) that can be visualized by immunolabeling (Moens et al 1997). These nucleoprotein filaments drive interchromosomal recombination, which is necessary for homolog pairing and synapsis in mice.…”

“…Recombination is initiated in leptonema by the formation of several hundred DSBs by the SPO11 protein. The induced DSBs are then resected to yield singlestranded 39 overhangs, which are bound by the singlestranded DNA (ssDNA)-binding trimeric protein complex RPA, which is hypothesized to aid in the processing and/or stabilization of the ssDNA ends and also D-loops of subsequent recombination intermediates (Luo et al 2013;Ribeiro et al 2016). Despite the synapsis defects, RPA2 decorated axial elements of zygotene-like mutant spermatocyte chromosomes in a pattern indistinguishable from wild-type, suggesting that meiotic DSBs were normally formed and resected in the absence of MCMDC2 ( Figure 4A).…”

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

“…The ssDNA tail is initially coated by the replication protein A (RPA) (reviewed in 183), protecting the potentially fragile ssDNA molecule and impairing secondary structure formation. RPA is gradually replaced by the RecA family members Rad51 and Dmc1, the latter being a meiosis-specific protein (16, 197, 201).…”