Abstract
The conserved ATPase, PCH-2/TRIP13, is required during both the spindle checkpoint and meiotic prophase. However, its specific role in regulating meiotic homolog pairing, synapsis and recombination has been enigmatic. Here, we report that this enzyme is required to proofread meiotic homolog interactions. We generated a mutant version of PCH-2 in C. elegans that binds ATP but cannot hydrolyze it: pch-2E253Q. In vitro, this mutant can bind a known substrate but is unable to remodel it. This mutation results in some non-homologous synapsis and impaired crossover assurance. Surprisingly, worms with a null mutation in PCH-2's adapter protein, CMT-1, the ortholog of p31comet, localize PCH-2 to meiotic chromosomes, exhibit non-homologous synapsis and lose crossover assurance. The similarity in phenotypes between cmt-1 and pch-2E253Q mutants suggest that PCH-2 can bind its meiotic substrates in the absence of CMT-1, in contrast to its role during the spindle checkpoint, but requires its adapter to hydrolyze ATP and remodel them.
Highlights
Sexual reproduction relies on meiosis, the specialized cell division that generates haploid gametes, such as sperm and eggs, from diploid progenitors so that fertilization restores diploidy
We previously showed that CMT-1 is required for PCH-2 to localize to mitotic chromosomes during the spindle checkpoint [66]
We show that the meiotic phenotypes observed in pch-2E253Q mutants are consistent with a role for PCH-2 in disassembling inappropriate pairing, synapsis and crossover recombination intermediates in C. elegans, PCH-2 proofreads meiotic homolog interactions resulting in non-homologous synapsis (Figs 3C, 3D and S1) and a loss of crossover assurance (Fig 4D)
Summary
Sexual reproduction relies on meiosis, the specialized cell division that generates haploid gametes, such as sperm and eggs, from diploid progenitors so that fertilization restores diploidy. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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