title: Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension.
abstract: It is well established that chromosome segregation in female meiosis I (MI) is error-prone. The acentrosomal meiotic spindle poles do not have centrioles and are not anchored to the cortex via astral microtubules. By Cre recombinase-mediated removal in oocytes of the microtubule binding site of nuclear mitotic apparatus protein (NuMA), which is implicated in anchoring microtubules at poles, we determine that without functional NuMA, microtubules lose connection to MI spindle poles, resulting in highly disorganized early spindle assembly. Subsequently, very long spindles form with hyperfocused poles. The kinetochores of homologs make attachments to microtubules in these spindles but with reduced tension between them and accompanied by alignment defects. Despite this, the spindle assembly checkpoint is normally silenced and the advance to anaphase I and first polar body extrusion takes place without delay. Females without functional NuMA in oocytes are sterile, producing aneuploid eggs with altered chromosome number. These findings establish that in mammalian MI, the spindle assembly checkpoint is unable to sustain meiotic arrest in the presence of one or few misaligned and/or misattached kinetochores with reduced interkinetochore tension, thereby offering an explanation for why MI in mammals is so error-prone.
authors.affiliation: Centre Interdisciplinaire de Recherche en Biologie, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 7241/Institut National de la Santé et de la Recherche Médicale U1050,  Collège de France, 75005 Paris,  France.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kolano
authors.forename: Stéphane
authors.initials: S
authors.lastname: Brunet
authors.forename: Alain D
authors.initials: AD
authors.lastname: Silk
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Verlhac
mesh_terms: D000705:Anaphase / Q000502:physiology; D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D020090:Chromosome Segregation / Q000502:physiology*; D005260:Female; D007247:Infertility, Female / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D018386:Kinetochores / Q000502:physiology*; D008322:Mammals; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008870:Microtubules / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D008941:Spindle Apparatus / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C489080:Numa1 protein, mouse