Meiotic Cohesion · Elucidating how chromosome cohesion is regulated and established during mammalian meiosis

Sister chromatid cohesion is essential for proper chromosome segregation. Chromosome cohesion is mediated by cohesin complexes which form a ring-like structure that embraces replicated sister chromatids and hold them together until anaphase onset. Although cohesin binds to DNA dynamically before S phase, cohesion is only established during DNA replication, which requires acetylation of cohesin complexes and subsequent recruitment of Sororin. Sororin promotes cohesion establishment and cohesion maintenance from S phase until mitosis by antagonizing Wapl. Maintenance of chromosome cohesion is extremely important in mammalian meiosis. In oocytes, cohesion establishment occurs during pre-meiotic S phase, which takes place before birth, and then has to be stably maintained until completion of meiosis, which only occurs several months or years later during ovulation. The mechanism responsible for meiotic cohesin stabilization for such long periods of time remains unclear. Notably, the increase of trisomies and other birth defects with maternal age correlates with a gradual loss of sister chromosome cohesion during oocyte maturation. Here, we intend to study how chromosome cohesion is established and regulated during meiosis and to unravel the detailed mechanism responsible for maintenance of sister chromatid cohesion for very long periods of time. We will additionally study how the dynamics of meiotic cohesin complexes affect homologous pairing and meiotic recombination.