The conserved AAA-ATPase PCH-2 distributes its regulation of meiotic prophase events by remodeling multiple meiotic HORMADs in C. elegans

During meiotic prophase, the essential events of pairing, synapsis, and recombination are coordinated with meiotic progression to promote fidelity and prevent aneuploidy. The conserved AAA+ ATPase PCH-2 controls a variety of chromosome behaviors, including coordinating pairing, synapsis and recombination between homologous chromosomes to guarantee crossover assurance and accurate chromosome segregation. However, how PCH-2 accomplishes this coordination is poorly understood. Here, we use a combination of genetic, cytological, and biochemical analyses to show that PCH-2 regulates pairing, synapsis and recombination in C. elegans by remodeling meiotic HORMADs from a closed conformation to an unlocked conformation. Further, we find PCH-2 coordinates these events by distributing this regulation among the three essential meiotic HORMADs in C. elegans: PCH-2 acts through HTP-3 to regulate pairing and synapsis, HIM-3 to promote crossover assurance, and HTP-1 to control meiotic progression. In addition to identifying a molecular mechanism for how PCH-2 regulates interhomolog interactions, our results provide a possible explanation for the expansion of this family as a conserved evolutionary feature of meiosis. Taken together, our work demonstrates that PCH-2’s well-characterized role in remodeling mitotic HORMADs applies to meiotic HORMADs and this remodeling coordinates homolog pairing, synapsis, recombination and meiotic progression to ensure accurate meiotic chromosome segregation.