Pch2 Links Chromosome Axis Remodeling at Future Crossover Sites and Crossover Distribution during Yeast Meiosis

Abstract

Segregation of homologous chromosomes during meiosis I depends on appropriately positioned crossovers/chiasmata. Crossover assurance ensures at least one crossover per homolog pair, while interference reduces double crossovers. Here, we have investigated the interplay between chromosome axis morphogenesis and non-random crossover placement. We demonstrate that chromosome axes are structurally modified at future crossover sites as indicated by correspondence between crossover designation marker Zip3 and domains enriched for axis ensemble Hop1/Red1. This association is first detected at the zygotene stage, persists until double Holliday junction resolution, and is controlled by the conserved AAA+ ATPase Pch2. Pch2 further mediates crossover interference, although it is dispensable for crossover formation at normal levels. Thus, interference appears to be superimposed on underlying mechanisms of crossover formation. When recombination-initiating DSBs are reduced, Pch2 is also required for viable spore formation, consistent with further functions in chiasma formation. pch2Δ mutant defects in crossover interference and spore viability at reduced DSB levels are oppositely modulated by temperature, suggesting contributions of two separable pathways to crossover control. Roles of Pch2 in controlling both chromosome axis morphogenesis and crossover placement suggest linkage between these processes. Pch2 is proposed to reorganize chromosome axes into a tiling array of long-range crossover control modules, resulting in chiasma formation at minimum levels and with maximum spacing. In the germ line of sexually reproducing organisms, haploid gametes are generated from diploid precursor cells by a specialized cell division called meiosis. Reduction by half of chromosome numbers during the first meiotic division depends on genetic exchange, resulting in the formation of crossovers. Without crossovers, pairs of homologous chromosomes frequently fail to separate, resulting in unbalanced gametes with a surplus or deficit of individual chromosomes. Along a given chromosome, crossovers form in different locations in different cells, but distribution of crossovers within each cell is controlled in two ways: first, at least one crossover is formed along each homolog pair, irrespective of size; second, a crossover in a given interval reduces the frequency of crossovers in adjacent chromosome regions. Here, we identify functions of the evolutionarily conserved protein Pch2 in suppressing additional crossovers in adjacent regions and ensuring homolog segregation under certain conditions. Pch2 further controls the assembly of chromosome axis protein Hop1 at future crossover sites. Our findings reveal that chromosome axes undergo structural changes at the same positions where crossovers occur. Thus, axis remodeling and crossover placement are linked via Pch2.