Sen, S.; Sarkar, S.; Menon, G.; Nambiar, M.

Centromere-proximal crossovers are repressed during meiosis across all species. However, there is a strong correlation between aberrant centromeric crossovers (C-COs) and the occurrence of meiotic aneuploidy and disorders such as Down syndrome. Despite decades of work in understanding repression of C-COs, the molecular basis of how they cause chromosomal mis-segregation is unknown. Here, we show that increased C-COs result in improper separation of homologs leading to increased meiosis I errors and aneuploidy in Schizosaccharomyces pombe. C-COs cause nondisjunction events that cannot be explained by random segregation of homologs and additionally, may also disrupt mono-orientation of sister chromatids in meiosis I leading to their premature separation. We provide evidence that the protected population of cohesins at centromeres during meiosis I may interfere with timely resolution of C-COs causing homolog nondisjunction. These molecular insights will improve our understanding of infertility and aneuploidy-associated developmental disorders in humans.