Search

Multiple meiosis-specific cohesion proteins act to facilitate homolog segregation at the first meiotic division. A recent paper demonstrates that meiotic cohesins can be separated into two complexes, one that establishes and maintains intersister cohesion and one that promotes interhomolog adhesion by regulating synaptonemal complex assembly.

In Drosophila, meiotic recombination is initiated by the formation of programmed DNA doublestrand breaks (DSBs), which occur within the context of the synaptonemal complex (SC). We created an in-frame deletion mutant in c(3)G (deleting amino acids L340 to N550, denoted as c(3)GccΔ1), which encodes the major transverse filament protein of the SC. Although c(3)GccΔ1 oocytes assemble full-length SC and exhibit normal DSB formation, euchromatic SC in both c(3)GccΔ1 heterozygotes and homozygotes precociously disassembles in early to mid pachytene. Centromeric SC, however, is unaffected in both genotypes. Thus, c(3)GccΔ1 is a separation-offunction mutant that establishes different functional and structural requirements between euchromatic and centromeric SC. Additionally, the chromosomes differ in their sensitivity to c(3)GccΔ1-induced perturbations in the SC. The X chromosome is distinctly sensitive to these perturbations, such that euchromatic pairing and crossing over are altered in c(3)GccΔ1 heterozygotes and severely reduced in c(3)GccΔ1 homozygotes. On the autosomes, crossovers are shifted to centromere-proximal regions and crossover interference is defective in both c(3)GccΔ1 homozygotes and heterozygotes. However, only c(3)GccΔ1 homozygotes display a progressive loss of euchromatic pairing in distal autosomal regions, suggesting that discontinuity in the euchromatic SC—rather than failed pairing—might cause the altered crossover distribution. These phenotypes reveal that different chromatin states or regions have differing requirements to maintain both the SC and homologous pairing. Furthermore, c(3)GccΔ1 is the first mutant in Drosophila to demonstrate that the SC appears to facilitate the regulation of recombination frequency and distribution differently on each chromosome.

Homologous recombination drives structural reorganization of the nucleus in early meiosis. In order to investigate the connection between homolog pairing, meiotic progression, and the dynamics of the underlying chromatin, we tracked flourescently labeled homolog pairs in synchronized S. cerevisae. Various previously unreported statistics of the anomalous inter-loci motion correlate with meiotic progression and can be quantitatively reproduced by a simple polymer model of the sister chromatids. The first of these is the distribution of waiting times for the homologous loci to come into and out of contact with each other (loosely, inter-locus “looping” and “unlooping” times). The full shape of the looping time distribution can be quantitatively reproduced by a simple model of two polymers diffusing independently in a spherical confinement. This finding suggests a dominant role for diffusion-limited, undirected search in homolog pairing in early meiosis. This is in sharp contrast with the intuition that a heavy-tailed search process could never drive such a critical cell-cycle stage. We further show that the inter-locus velocity-velocity correlation (VVC) quantitatively matches analytical results for the inter-locus VVC of our polymer model, allowing us to leverage our analytical theory to extract the time scale of stress communication between the labeled loci along the chromosome. We show that stresses can take tens of minutes to propagate between loci on paired chromosomes, and that the increasing connectivity between the chromosomes as the cell progresses through meiosis can be quantified by the shortening of this communication time. Our study highlights the power of coarse-grained polymer models to analyze dynamic structural properties of the nucleus in vivo and the importance of analytical theory for uncovering intracellular connections that might be obscured by lag times of many minutes.