Pseudosynapsis and Decreased Stringency of Meiotic Repair Pathway Choice on the Hemizygous Sex Chromosome of Caenorhabditis elegans Males

Abstract

During meiosis, accurate chromosome segregation relies on homology to mediate chromosome pairing, synapsis, and crossover recombination. Crossovers are dependent upon formation and repair of double-strand breaks (DSBs) by homologous recombination (HR). In males of many species, sex chromosomes are largely hemizygous, yet DSBs are induced along nonhomologous regions. Here we analyzed the genetic requirements for meiotic DSB repair on the completely hemizygous X chromosome of Caenorhabditis elegans males. Our data reveal that the kinetics of DSB formation, chromosome pairing, and synapsis are tightly linked in the male germ line. Moreover, DSB induction on the X is concomitant with a brief period of pseudosynapsis that may allow X sister chromatids to masquerade as homologs. Consistent with this, neither meiotic kleisins nor the SMC-5/6 complex are essential for DSB repair on the X. Furthermore, early processing of X DSBs is dependent on the CtIP/Sae2 homolog COM-1, suggesting that as with paired chromosomes, HR is the preferred pathway. In contrast, the X chromosome is refractory to feedback mechanisms that ensure crossover formation on autosomes. Surprisingly, neither RAD-54 nor BRC-2 are essential for DSB repair on the X, suggesting that unlike autosomes, the X is competent for repair in the absence of HR. When both RAD-54 and the structure-specific nuclease XPF-1 are abrogated, X DSBs persist, suggesting that single-strand annealing is engaged in the absence of HR. Our findings indicate that alteration in sister chromatid interactions and flexibility in DSB repair pathway choice accommodate hemizygosity on sex chromosomes.

SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes

“…SMC5/6 was also visible along chromosome axes at pachynema in oocytes, which was also detected in mouse spermatocytes (Gomez et al, 2013). In addition, transient foci of SMC6 were detected along the chromosome arms in female germ cells during pachynema, suggesting a role during meiotic recombination, which has previously been reported using budding yeast and Caenorhabditis elegans (Bickel et al, 2010;Hong et al, 2016;Checchi et al, 2014;Copsey et al, 2013;Lilienthal et al, 2013;Xaver et al, 2013). In mammals, every chromosome pair obtains many recombination sites but generally yields only one to two crossover sites (Kauppi et al, 2004).…”

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

“…To confirm that the chromosome lacking H3K4me2 in male germ cells was indeed the X, we examined the loading of SYP-1 or SYP-2, central region components of the SC, which are not present on the X chromosome in pachytene nuclei in C. elegans male germ cells (Jaramillo-Lambert and Engebrecht 2010; Checchi et al 2014). To that end, we used antibodies raised against C. elegans SYP-1 or SYP-2 peptide sequences with strong sequence identity to the corresponding proteins in the different species (Materials and Methods).…”

The Genetics of Sex: Exploring Differences

“…Furthermore, male and female gametes are morphologically distinct and undergo meiosis at different times during their developmental trajectories. Checchi et al (2014) examined the mechanisms that ensure segregation of the hemizygous X chromosome in C. elegans males (XO). They demonstrate that double-strand DNA breaks (DSB) are important for segregation of the hemizygous X and present evidence that DSBs could mediate sister chromatid synapsis (pseudosynapsis), instead of the typical synapses formed between homologs.…”

“…Two other articles examine differences in the evolution of sex chromosomes: Blackmon and Demuth (2014) look at the evolutionary turnover of sex chromosomes in beetles and Kirkpatrick and Guerrero (2014) use the recombining region of sex chromosomes to measure the strength of sexually antagonistic selection. Finally, two studies focus on gametogenesis-sex differences in meiosis in Caenorhabditis elegans (Checchi et al 2014) and the specification and development of germinal cells in maize (Zhang et al 2014).…”