title: Restaging the spindle assembly checkpoint in female mammalian meiosis I.
abstract: In mammalian somatic cells, the spindle assembly checkpoint (SAC) is indispensable for ensuring the fidelity of chromosome segregation by delaying cell-cycle progression in the face of even a single misaligned chromosome. In contrast, the role of the SAC in unperturbed mammalian oocytes is less well defined as progression through meiosis I is unaltered in mouse oocytes in the presence of one or a few misaligned chromosomes. Furthermore, attempts to disable the function of the SAC protein, Mad2, in mouse oocytes have produced conflicting results. To gain further insight into SAC function during female mammalian meiosis I, we recently utilised a morpholino-based antisense approach to deplete the majority of Mad2 in mouse oocytes. Our results define a clear role for Mad2 in ensuring the proper timing of meiosis I events and ultimately, in ensuring the fidelity of homologue disjunction. We discuss the implications of these results for the regulation of meiosis I in mammalian oocytes and for the genesis of human aneuploidy.
authors.affiliation: Newcastle Fertility Centre at Life, Centre for Life, Times Square, Newcastle upon Tyne, UK. h.a.homer@ncl.ac.uk
authors.forename: Hayden A
authors.initials: HA
authors.lastname: Homer
authors.forename: Alex
authors.initials: A
authors.lastname: McDougall
authors.forename: Mark
authors.initials: M
authors.lastname: Levasseur
authors.forename: Mary
authors.initials: M
authors.lastname: Herbert
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D000782:Aneuploidy; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000032:analysis / Q000502:physiology*; D019926:Cyclin B / Q000032:analysis / Q000502:physiology; D005260:Female; D006801:Humans; D064246:Mad2 Proteins; D049469:Meiotic Prophase I / Q000502:physiology*; D051379:Mice; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins / Q000032:analysis / Q000502:physiology; D009865:Oocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D009866:Oogenesis / Q000502:physiology*; D064249:Securin; D008941:Spindle Apparatus / Q000502:physiology*; D043743:Ubiquitin-Protein Ligase Complexes / Q000032:analysis / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; D009687:Nuclear Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome