Meiosis in human females is associated with a surprisingly high incidence of errors leading to aneuploidy, which is a major cause of pregnancy loss. Accurate segregation of chromosomes in meiosis requires a sequential removal of cohesin complexes, holding together sister chromatids. The cohesin on chromosome arms, involved in the separation of homologues, is dissolved during first meiosis whereas centromeric cohesin is removed during second meiosis, coincidentally with separation of the sister chromatids. H owever, the enzyme cleaving Scc1-like cohesin subunit called separase is active in both divisions, therefore the centromeric cohesin must be somehow refractory to the cleavage during meiosis I. Protein called shugoshin or Sgo1 was recently linked to protec tion of centromeric cohesion during meiosis in Drosophila and yeasts and during mitosis in mammals.The aim of the proposed study is to elucidate the molecular mechanism of protection of centromeric cohesion during meiosis in mammals. Since it is still uncl ear whether the yeast model also applies to mammals, we will identify cohesin subunits mediating sister chromatid cohesion in mouse meiosis. Conditional knockout of Sgo1 in oocytes will elucidate a potential role of this molecule in protection of centromer ic cohesin. Our results will greatly aid understanding to the molecular mechanisms underlying chromosome segregation in mammalian meiosis.
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