ZHP-3 Acts at Crossovers to Couple Meiotic Recombination with Synaptonemal Complex Disassembly and Bivalent Formation in C. elegans

Abstract

Crossover recombination and the formation of chiasmata normally ensure the proper segregation of homologous chromosomes during the first meiotic division. zhp-3, the Caenorhabditis elegans ortholog of the budding yeast ZIP3 gene, is required for crossover recombination. We show that ZHP-3 protein localization is highly dynamic. At a key transition point in meiotic prophase, the protein shifts from along the length of the synaptonemal complex (SC) to an asymmetric localization on the SC and eventually becomes restricted to foci that mark crossover recombination events. A zhp-3::gfp transgene partially complements a null mutation and reveals a separation of function; although the fusion protein can promote nearly wild-type levels of recombination, aneuploidy among the progeny is high, indicating defects in meiotic chromosome segregation. The structure of bivalents is perturbed in this mutant, suggesting that the chromosome segregation defect results from an inability to properly remodel chromosomes in response to crossovers. smo-1 mutants exhibit phenotypes similar to zhp-3::gfp mutants at higher temperatures, and smo-1; zhp-3::gfp double mutants exhibit more severe meiotic defects than either single mutant, consistent with a role for SUMO in the process of SC disassembly and bivalent differentiation. We propose that coordination of crossover recombination with SC disassembly and bivalent formation reflects a conserved role of Zip3/ZHP-3 in coupling recombination with SC morphogenesis. Sexual reproduction relies on meiosis. This specialized cell division generates gametes, such as sperm and eggs, with a single copy of the genome, so that fertilization restores diploidy. In order for chromosomes to segregate correctly during meiosis, homologs usually must undergo crossing over (genetic exchange) during meiotic prophase. How crossovers are coupled to large-scale changes in chromosome structure is not well understood. Our work shows that the protein ZHP-3 localizes to crossovers late in prophase, coincident with a transition in which chromosomes initiate progressive restructuring around the crossover. We have found that a ZHP-3-GFP fusion protein is competent to promote genetic exchange but not proper segregation. Chromosomes from these mutant animals exhibit defects in this late-prophase restructuring, suggesting that alterations in chromosome architecture that typically accompany crossovers have not occurred. We propose that ZHP-3 acts at crossovers to coordinate genetic exchange with higher order changes in chromosome structure that promote proper chromosome segregation.