Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes

Gui, Liming and Homer, Hayden (2012) Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes. Development, 139 11: 1941-1946. doi:10.1242/dev.078352

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Author Gui, Liming
Homer, Hayden
Title Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes
Journal name Development   Check publisher's open access policy
ISSN 0950-1991
Publication date 2012-06-01
Year available 2012
Sub-type Article (original research)
DOI 10.1242/dev.078352
Open Access Status File (Publisher version)
Volume 139
Issue 11
Start page 1941
End page 1946
Total pages 6
Place of publication Cambridge, United Kingdom
Publisher The Company of Biologists
Language eng
Abstract The spindle assembly checkpoint (SAC) averts aneuploidy by coordinating proper bipolar chromosomal attachment with anaphase-promoting complex/cyclosome (APC/C)-mediated securin and cyclin B1 destruction required for anaphase onset. The generation of a Mad2-based signal at kinetochores is central to current models of SAC-based APC/C inhibition. During mitosis, kinetochores of polar-displaced chromosomes, which are at greatest risk of mis-segregating, recruit the highest levels of Mad2, thereby ensuring that SAC activation is proportionate to aneuploidy risk. Paradoxically, although an SAC operates in mammalian oocytes, meiosis I (MI) is notoriously error prone and polar-displaced chromosomes do not prevent anaphase onset. Here we find that Mad2 is not preferentially recruited to the kinetochores of polar chromosomes of wild-type mouse oocytes, in which polar chromosomes are rare, or of oocytes depleted of the kinesin-7 motor CENP-E, in which polar chromosomes are more abundant. Furthermore, in CENP-E-depleted oocytes, although polar chromosomal displacement intensified during MI and the capacity to form stable end-on attachments was severely compromised, all kinetochores nevertheless became devoid of Mad2. Thus, it is possible that the ability of the SAC to robustly discriminate chromosomal position might be compromised by the propensity of oocyte kinetochores to become saturated with unproductive attachments, thereby predisposing to aneuploidy. Our data also reveal novel functions for CENP-E in oocytes: first, CENP-E stabilises BubR1, thereby impacting MI progression; and second, CENP-E mediates bi-orientation by promoting kinetochore reorientation and preventing chromosomal drift towards the poles.
Keyword Aneuploidy
CENP-E
Mad2
Meiosis I
Mouse oocytes
Spindle assembly checkpoint
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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