Dynamic molecular architecture of the synaptonemal complex

Abstract

During meiosis, chromosomes pair with their homologous partners, and a structure known as the synaptonemal complex (SC) assembles between them. Evidence indicates that this material plays a role in regulating crossover recombination between homologs, although this remains controversial. Here we use three-dimensional STochastic Optical Reconstruction Microscopy (3D-STORM) to interrogate the molecular architecture of the SC in intact germline tissue from Caenorhabditis elegans, and analyze its ultrastructure during meiotic progression. Using a probabilistic mapping approach, we determine the position and orientation of the four known SC structural proteins. We report that a marked structural transition occurs within this material upon crossover designation. We also identify a mutation that disturbs both SC ultrastructure and crossover interference, the widespread mechanism that results in non-randomly wide spacing of crossovers between the same chromosome pair. Together with other evidence, our findings suggest that the SC is an active material, and that structural transitions may directly contribute to chromosome-wide crossover regulation.

Synaptonemal Complex dimerization regulates chromosome alignment and crossover patterning in meiosis

“…Our work also strengthens the idea that, at least in C. elegans, the SC directly mediates crossover interference. Perturbations of the SC -including partial depletion and mutations in syp-1, -4, -5 and -6 ( [4,11,13] and this work) -weaken crossover interference. The exact signal that spreads along entire chromosomes to mediate interference remains elusive, but diffusion within a liquid SC has been proposed as a mechanism for how signals might be propagated [18].…”

“…The SC (green) holds the two homologs in alignment. Right, the stereotypic organization of SC components (from [12,13,15,16] intensity inside the chromosome mask by the sum intensity outside the mask, and normalizing by the enrichment value for HTP-3-wrmScarlet. The bars indicate the median enrichment, and the boxes indicate the middle 50%.…”

“…The SC is composed of a handful of subunits (six in C. elegans [7][8][9][10][11][12]) that occupy stereotypic locations relative to the axes ( Fig. 1A; [12][13][14][15][16]). However, we have limited understanding of how SC proteins interact with one another, or how their structure helps them to carry out functions such as aligning the homologs or regulating crossovers.…”

“…However, while several genetic perturbations in C. elegans cause the SC to be associated with all chromosomes without holding paired axes together [10,27,28], the molecular details underlying pairing interactions have not been elucidated. Likewise, despite the identification of conditions that decrease crossover interference -mutations in the C-termini of syp-4, -5 and -6, and partial depletion of SC components [4,11,13] -the molecular mechanisms that generate this chromosome-scale phenotype remain unknown.…”

“…To gain mechanistic insight into SC functions, we randomly mutagenized an N-terminal stretch of the SC component SYP-1, which localizes to the middle of the SC ( Fig. 1A; [5,13,15]). Detailed analyses of the separation-of-function mutations that we isolated showed that the Nterminus of SYP-1 is critical for the coupling of SC assembly and chromosome alignment, as well as for the regulation of crossovers.…”