- Title
- Timing of anaphase-promoting complex activation in mouse oocytes is predicted by microtubule-kinetochore attachment but not by bivalent alignment or tension
- Creator
- Lane, Simon I. R.; Yun, Yan; Jones, Keith T.
- Relation
- NHMRC.569202 | ARC|DP120100946
- Relation
- Development: for advances in developmental biology and stem cells Vol. 139, Issue 11, p. 1947-1955
- Publisher Link
- http://dx.doi.org/10.1242/dev.077040
- Publisher
- The Company of Biologists
- Resource Type
- journal article
- Date
- 2012
- Description
- Homologous chromosome segregation errors during meiosis I are common and generate aneuploid embryos. Here, we provide a reason for this susceptibility to mis-segregation by live cell imaging of mouse oocytes. Our results show that stable kinetochore-microtubule attachments form in mid-prometaphase, 3-4 hours before anaphase. This coincided with the loss of Mad2 from kinetochores and with the start of anaphase-promoting complex/cyclosome (APC/C)-mediated cyclin B1 destruction. Therefore, the spindle assembly checkpoint (SAC) ceased to inhibit the APC/C from mid-prometaphase. This timing did not coincide with bivalent congression in one-third of all oocytes examined. Non-aligned bivalents were weakly positive for Mad2, under less tension than congressed bivalents and, by live-cell imaging, appeared to be in the process of establishing correct bi-orientation. The time from when the APC/C became active until anaphase onset was affected by the rate of loss of CDK1 activity, rather than by these non-aligned bivalents, which occasionally persisted until anaphase, resulting in homolog non-disjunction. We conclude that, in oocytes, a few erroneous attachments of bivalent kinetochores to microtubules do not generate a sufficient SAC ‘wait anaphase’ signal to inhibit the APC/C.
- Subject
- aneuploidy; SAC satisfaction; spindle assembly checkpoint (SAC); Down Syndrome
- Identifier
- http://hdl.handle.net/1959.13/1321063
- Identifier
- uon:24259
- Identifier
- ISSN:0950-1991
- Language
- eng
- Full Text
- Reviewed
- Hits: 5965
- Visitors: 2170
- Downloads: 387
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 1 MB | Adobe Acrobat PDF | View Details Download |