Meiosis-Specific Cohesin in Mammalian Germ Cells

Abstract

Meiosis requires specialized mechanisms to coordinate chromosome pairing, recombination, and stepwise chromosome segregation. Central to these processes are cohesin complexes that incorporate meiosis-specific subunits, including SMC1β, REC8, RAD21L, and STAG3. Unlike canonical mitotic cohesin, these variants endow germ cells with distinct regulatory properties that ensure durable sister chromatid cohesion, promote homolog interactions, and establish the unique segregation patterns of meiosis I and II. Genetic and cytological studies have revealed that individual kleisin subunits perform non-redundant functions: REC8 provides the primary replication-coupled cohesion essential for chromosome axis integrity, whereas RAD21L supports homolog pairing and recombination through mechanisms linked to double-strand break formation. At centromeres, protected cohesin complexes cooperate with shugoshin–PP2A to preserve cohesion and define kinetochore orientation, thereby enabling reductional division. A remarkable feature of mammalian oocytes is the extraordinary longevity of meiotic cohesin, which must be maintained for years to decades without efficient turnover. Age-dependent deterioration of this cohesion machinery represents a major source of chromosome mis-segregation, contributing to infertility, miscarriage, and congenital aneuploidies. In this Review, we focus on the molecular composition, regulation, and functional specialization of meiosis-specific cohesins in mammalian germ cells. We integrate recent genetic, biochemical, and imaging studies to discuss how distinct cohesin complexes partition tasks during prophase, how cohesion is protected at centromeres, and how cohesin failure underlies reproductive aging and disease.