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Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension

Kolano, Agnieszka ; Brunet, Stéphane ; Silk, Alain D ; Cleveland, Don W ; Verlhac, Marie-Hélène

Proceedings of the National Academy of Sciences - PNAS, 2012-07, Vol.109 (27), p.E1858-E1867 [Periódico revisado por pares]

United States: National Acad Sciences

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Título:
Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension
Autor: Kolano, Agnieszka ; Brunet, Stéphane ; Silk, Alain D ; Cleveland, Don W ; Verlhac, Marie-Hélène
Assuntos: Anaphase - physiology ; Aneuploidy ; Animals ; Binding sites ; Biological Sciences ; Cells, Cultured ; Cellular Biology ; Chromosome Segregation - physiology ; Chromosomes ; Female ; Infertility, Female - genetics ; Infertility, Female - metabolism ; Infertility, Female - physiopathology ; Kinetochores - physiology ; Life Sciences ; Mammals ; Meiosis - physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Microtubules - physiology ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Oocytes - cytology ; Oocytes - physiology ; PNAS Plus ; Signal Transduction - physiology ; Spindle Apparatus - physiology ; Stress, Mechanical ; Subcellular Processes
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2012-07, Vol.109 (27), p.E1858-E1867
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PMCID: PMC3390881
Contributed by Don W. Cleveland, March 20, 2012 (sent for review January 7, 2012)
Author contributions: A.K. and M.-H.V. designed research; A.K. and S.B. performed research; A.D.S. and D.W.C. contributed new reagents/analytic tools; A.K., S.B., D.W.C., and M.-H.V. analyzed data; and A.K., S.B., A.D.S., D.W.C., and M.-H.V. wrote the paper.
Descrição: 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.
Editor: United States: National Acad Sciences
Idioma: Inglês

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Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension

Kolano, Agnieszka ; Brunet, Stéphane ; Silk, Alain D ; Cleveland, Don W ; Verlhac, Marie-Hélène

United States: National Acad Sciences

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