Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension
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 nucl...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 27; pp. E1858 - E1867 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Acad Sciences
03.07.2012
National Academy of Sciences |
Series | PNAS Plus |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | 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. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1204686109 |