Loss of meiotic double strand breaks triggers recruitment of recombination-independent pro-crossover factors in C. elegans spermatogenesis

Abstract

A key event in meiosis is the conversion of a small subset of double strand breaks into interhomolog crossovers. In this study, we demonstrate that Caenorhabditis elegans male spermatogenesis has less robust mechanisms than hermaphrodite oogenesis for ensuring and limiting the conversion of double strand breaks into crossovers. This is not a consequence of differences in meiotic prophase timing, sex chromosome genotype, or the presence or absence of germline apoptosis. Using the cyclin-like crossover marker COSA-1, we show that males have a linear response in converting increasing numbers of double strand breaks into crossovers, suggesting weakened crossover homeostasis. While the topoisomerase SPO-11, responsible for initiating meiotic double strand breaks, has an extended period of activity in males as in hermaphrodites, we discovered that COSA-1 foci form at the very end of meiotic prophase in the absence of SPO-11 during spermatogenesis. These COSA-1-marked sites are also independent of homologous recombination, and Topoisomerases I and II. We find that the synaptonemal complex, which holds homologs in proximity, differently modulates COSA-1 enrichment to chromosomes in the absence of SPO-11 in males and hermaphrodites. Together, these findings suggest that males have less robust crossover control and that there are previously unrecognized lesions or structures at the end of meiotic prophase in spermatocytes that can accumulate CO markers. Author SummaryFormation of healthy gametes depends on the accurate partitioning of genetic material in the daughter cells through meiosis. A hallmark of meiosis is the establishment of crossovers, which arise from physical exchange of DNA between the parental chromosomes during homologous recombination. Recombination is initiated via the induction of physiological DNA damage by the topoisomerase SPO-11 and its auxiliary factors. Abrogating SPO-11 activity prevents crossover formation, resulting in random chromosome segregation and generation of aneuploid gametes. While the underlying mechanisms of crossover formation are conserved between the sexes, several pieces of evidence indicate extensive sexual dimorphism. In our work we describe novel features of C. elegans spermatogenesis that reveal significant differences in the regulation of recombination compared to oogenesis. We find that in spermatogenesis crossover-promoting proteins can be recruited to chromosomes even in the absence of SPO-11 activity, a phenomenon not observed in the oogenic hermaphrodite germ line. Furthermore, removal of some auxiliary factors required for physiological break formation during oogenesis does not prevent crossover designation in spermatocytes. We show that the synaptonemal complex, tasked with keeping homologous chromosomes in proximity, exerts opposing roles in males and hermaphrodites by promoting and limiting the recruitment of SPO-11-independent crossover factors, respectively.