Cohesin variants and meiotic timing shape chromosome segregation accuracy.

The frequency of aneuploid gamete formation increases with maternal age, yet the effects of genetic variants on meiotic chromosome segregation accuracy during aging remain poorly understood. Using the multicellular organism Caenorhabditis elegans, we investigate the impact of mutations in the conserved cohesin complex on age-associated meiotic errors. Point mutations in the head domain of the cohesin component SMC-1, which alter local hydrophobicity, cause meiotic defects that vary with age. A severe mutation causes incomplete synapsis and defective crossover formation, and a minor one causes age-related diakinesis bivalent abnormalities. Notably, while the mild mutation causes defects only in aged worms, worms with the severe mutation exhibit significantly alleviated phenotypes with age. Genetic and cytological analyses suggest that this alleviation results from a slowed meiotic progression during early prophase, which restores impaired cohesin loading. These findings reveal that cohesin variants, meiotic progression speed during early prophase, and the overall duration of meiosis collectively shape the accuracy of meiotic chromosome segregation.