title: Spindle assembly checkpoint of oocytes depends on a kinetochore structure determined by cohesin in meiosis I.
abstract: Since the dissolution of sister chromatid cohesion by separase and cyclin B destruction is irreversible, it is essential to delay both until all chromosomes have bioriented on the mitotic spindle. Kinetochores that are not correctly attached to the spindle generate the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex/cyclosome (APC/C) and blocks anaphase onset. This process is known as the spindle assembly checkpoint (SAC). The SAC is especially important in meiosis I, where bivalents consisting of homologous chromosomes held together by chiasmata biorient. Since the first meiotic division is unaffected by rare achiasmatic chromosomes or misaligned bivalents, it is thought that several tensionless kinetochores are required to produce sufficient MCC for APC/C inhibition. Consistent with this, univalents lacking chiasmata elicit a SAC-mediated arrest in Mlh1(-/-) oocytes. In contrast, chromatids generated by TEV protease-induced cohesin cleavage in Rec8(TEV/TEV) oocytes merely delay APC/C activation. Since the arrest of Mlh1(-/-)Rec8(TEV/TEV) oocytes is alleviated by TEV protease, even when targeted to kinetochores, we conclude that their SAC depends on cohesin as well as dedicated kinetochore proteins. This has important implications for aging oocytes, where cohesin deterioration will induce sister kinetochore biorientation and compromise MCC production, leading to chromosome missegregation and aneuploid fetuses.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: kikue.tachibana@imba.oeaw.ac.at.
authors.forename: Kikuë
authors.initials: K
authors.lastname: Tachibana-Konwalski
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Godwin
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Máté
authors.initials: M
authors.lastname: Borsos
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Rattani
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: kim.nasmyth@bioch.ox.ac.uk.
authors.forename: Kim
authors.initials: K
authors.lastname: Nasmyth
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002842:Chromatids / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018386:Kinetochores / Q000502:physiology / Q000648:ultrastructure*; D059566:M Phase Cell Cycle Checkpoints; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000166:cytology*; D059008:Time-Lapse Imaging; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins