A quality control mechanism coordinates meiotic prophase events to promote crossover assurance.
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.
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Alison J
AJ
Deshong
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Alice L
AL
Ye
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Piero
P
Lamelza
Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Needhi
N
Bhalla
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics; D023902:Chromosome Pairing / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D002875:Chromosomes / Q000235:genetics; D003434:Crossing Over, Genetic / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D008540:Meiosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011418:Prophase / Q000235:genetics*; D011786:Quality Control
D029742:Caenorhabditis elegans Proteins; D009687:Nuclear Proteins