Specialization of chromosome segregation mechanisms in meiosis

Meiosis generates gametes with half the parental genome through two consecutive chromosome segregation events, meiosis I and meiosis II. Meiotic errors are prevalent in humans, accounting for frequent miscarriages, birth defects and infertility, yet the mechanistic origins of these errors are undefined. Our vision is to discover the molecular basis of the adaptations that sort chromosomes into gametes during meiosis. We will exploit the tractability of yeast meiosis to overcome the limitations of protracted meiosis and scarcity of material in other systems, to address three complementary aims. First, we will determine the mechanism by which kinetochores suppress crossover recombination near centromeres during meiotic prophase, and the significance of this suppression for chromosome segregation. Second, we will reveal how sister kinetochores are specifically fused, and the surveillance machinery re-wired, to permit sister chromatid co-segregation only during meiosis I. Third, we will identify the modified cell cycle controls that drive two consecutive chromosome segregation events during meiosis and determine how these controls couple chromosome morphogenesis to gametogenesis. The molecular pathways we discover will provide a framework for identifying potential sources of meiotic errors in humans.