A quality control mechanism coordinates meiotic prophase events to promote crossover assurance.
A quality control mechanism coordinates meiotic prophase events to promote crossover assurance.
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DOI：
10.1371/journal.pgen.1004291
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发表时间：
2014-04
期刊：
影响因子：
4.5
通讯作者：
Bhalla N
中科院分区：
文献类型：
--
作者：
Deshong AJ;Ye AL;Lamelza P;Bhalla N
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. The production of sperm and eggs for sexual reproduction depends on meiosis. During this specialized cell division, homologous chromosomes are linked by at least one crossover recombination event, or chiasma, to promote their proper segregation. How events in meiotic prophase are coordinated to contribute to crossover assurance is not well understood. Here, we show that C. elegans PCH-2 regulates a variety of events during meiotic prophase to promote crossover assurance. In the absence of pch-2, pairing, synapsis and recombination are accelerated, resulting in defects in synapsis and crossover formation. We propose that PCH-2 restrains the events of meiotic prophase to coordinate them, ensure their fidelity and guarantee that each homolog pair has at least one crossover to promote proper meiotic chromosome segregation.
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