PCH-2 collaborates with CMT-1 to proofread meiotic homolog interactions

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-2^E253Q. 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 p31^comet, localize PCH-2 to meiotic chromosomes, exhibit non-homologous synapsis and lose crossover assurance. The similarity in phenotypes between cmt-1 and pch-2^E253Q 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. The production of sperm and eggs for sexual reproduction depends on meiosis. During this specialized cell division, homologous chromosomes pair, synapse and undergo meiotic recombination so that they are linked by at least one chiasma to promote their proper segregation. How homologous chromosomes ensure that these important interactions are with the correct partner is currently unknown. Here, we show that PCH-2 and its adapter protein, CMT-1, proofread homolog interactions to promote their fidelity and proper meiotic chromosome segregation.