RRC ID 45721
著者 Deshong AJ, Ye AL, Lamelza P, Bhalla N.
タイトル A quality control mechanism coordinates meiotic prophase events to promote crossover assurance.
ジャーナル PLoS Genet
Abstract Meiotic chromosome segregation relies on homologous chromosomes being linked by at least one crossover, the obligate crossover. Homolog pairing, synapsis and meiosis specific DNA repair mechanisms are required for crossovers but how they are coordinated to promote the obligate crossover is not well understood. PCH-2 is a highly conserved meiotic AAA+-ATPase that has been assigned a variety of functions; whether these functions reflect its conserved role has been difficult to determine. We show that PCH-2 restrains pairing, synapsis and recombination in C. elegans. Loss of pch-2 results in the acceleration of synapsis and homolog-dependent meiotic DNA repair, producing a subtle increase in meiotic defects, and suppresses pairing, synapsis and recombination defects in some mutant backgrounds. Some defects in pch-2 mutants can be suppressed by incubation at lower temperature and these defects increase in frequency in wildtype worms grown at higher temperature, suggesting that PCH-2 introduces a kinetic barrier to the formation of intermediates that support pairing, synapsis or crossover recombination. We hypothesize that this kinetic barrier contributes to quality control during meiotic prophase. Consistent with this possibility, defects in pch-2 mutants become more severe when another quality control mechanism, germline apoptosis, is abrogated or meiotic DNA repair is mildly disrupted. PCH-2 is expressed in germline nuclei immediately preceding the onset of stable homolog pairing and synapsis. Once chromosomes are synapsed, PCH-2 localizes to the SC and is removed in late pachytene, prior to SC disassembly, correlating with when homolog-dependent DNA repair mechanisms predominate in the germline. Indeed, loss of pch-2 results in premature loss of homolog access. Altogether, our data indicate that PCH-2 coordinates pairing, synapsis and recombination to promote crossover assurance. Specifically, we propose that the conserved function of PCH-2 is to destabilize pairing and/or recombination intermediates to slow their progression and ensure their fidelity during meiotic prophase.
巻・号 10(4)
ページ e1004291
公開日 2014-4-1
DOI 10.1371/journal.pgen.1004291
PII PGENETICS-D-13-02320
PMID 24762417
PMC PMC3998905
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Cell Nucleus / genetics Chromosome Pairing / genetics Chromosome Segregation / genetics Chromosomes / genetics Crossing Over, Genetic / genetics* DNA Repair / genetics Meiosis / genetics* Mutation / genetics Nuclear Proteins / genetics Prophase / genetics* Quality Control
IF 5.175
引用数 14
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm1866 tm1458