Objectif 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. Champ scientifique natural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesgeneticshereditynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Mots‑clés APC Rec8 Scc1 Sgo1 centromere chromosome segregation cohesin separase shugoshin Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Thème(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Appel à propositions FP6-2004-MOBILITY-5 Voir d’autres projets de cet appel Régime de financement EIF - Marie Curie actions-Intra-European Fellowships Coordinateur THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Contribution de l’UE Aucune donnée Adresse University Offices, Wellington Square OXFORD Royaume-Uni Voir sur la carte Liens Site web Opens in new window Coût total Aucune donnée
