Chromosome Sites Play Dual Roles to Establish Homologous Synapsis during Meiosis in C. elegans

Abstract

We have investigated the role of pairing centers (PCs), cis-acting sites required for accurate segregation of homologous chromosomes during meiosis in C. elegans. We find that these sites play two distinct roles that contribute to proper segregation. Chromosomes lacking PCs usually fail to synapse and also lack a synapsis-independent stabilization activity. The presence of a PC on just one copy of a chromosome pair promotes synapsis but does not support synapsis-independent pairing stabilization, indicating that these functions are separable. Once initiated, synapsis is highly processive, even between nonhomologous chromosomes of disparate lengths, elucidating how translocations suppress meiotic recombination in C. elegans. These findings suggest a multistep pathway for chromosome synapsis in which PCs impart selectivity and efficiency through a "kinetic proofreading" mechanism. We speculate that concentration of these activities at one region per chromosome may have coevolved with the loss of a point centromere to safeguard karyotype stability.

Manipulation of Karyotype inCaenorhabditis elegansReveals Multiple Inputs Driving Pairwise Chromosome Synapsis During Meiosis

“…The following primary antibodies were used: chicken anti-HTP-3 (1:250, MacQueen et al 2005), rabbit anti-GFP (1:1000, Yokoo et al 2012), rabbit anti-SYP-1 (1:250, MacQueen et al 2002), and guinea pig anti-HIM-8 (1:250, Phillips et al 2005). Secondary antibodies were Alexa Fluor 488-, 555-, and 647-conjugated goat antibodies directed against the appropriate species (1:400, Life Technologies).…”

“…This powerful combination of genetics and cytology has enabled discovery of a complex network of factors regulating homolog pairing and synapsis. These include specialized chromosomal sites called "pairing centers" (PCs), located near one end of each chromosome (Rosenbluth and Baillie 1981;Rose et al 1984;McKim et al 1988McKim et al , 1993Villeneuve 1994), that mediate chromosome movements that are important both for achieving timely homolog pairing and for constraining SC assembly to occur exclusively between correctly paired homologs (MacQueen et al 2005;MartinezPerez and Villeneuve 2005;Phillips et al 2005;Penkner et al 2007Penkner et al , 2009Sato et al 2009).…”

Broad chromosomal domains of histone modification patterns in C. elegans

“…C. elegans does not have a defined centromeric locus on each chromosome; instead, the chromosomes are holocentric, with centromeric function distributed along the length of each chromosome (Albertson and Thomson 1982;Maddox et al 2004). During meiosis, a special region near one end of each chromosome, known as a ''Homolog Recognition Region'' or ''Pairing Center,'' mediates pairing and synapsis between homologous chromosomes through interactions with components of the nuclear envelope (MacQueen et al 2005;Phillips et al 2005;Phillips and Dernburg 2006). Meiotic crossover recombination is elevated on both distal regions or ''arms'' of the five autosomes, which are enriched for repeated sequences and where genes are more sparse and introns are relatively large compared to the central region of the chromosome (Barnes et al 1995; The C. elegans Sequencing Consortium 1998; Prachumwat et al 2004).…”

Synaptonemal complex extension from clustered telomeres mediates full-length chromosome pairing in Schmidtea mediterranea

“…Similarly, in Caenorhabditis elegans, DSBs are not required for synapsis (16). Rather, pairing is initiated at telomereadjacent pairing centers (PCs) on each homolog pair, and the processive extension of SC from the PCs is required to establish the alignment of homologous chromosomes along their full lengths (17,18). As opposed to its much later role(s) in mammals and yeast, the SC in these systems appears to be critical for establishing tight pairing and maintaining tight homolog associations, thus providing an environment in which DSBs can mature into functional crossovers.…”