- Title
- APC FZR1 prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing
- Creator
- Holt, Jane E.; Lane, Simon I. R.; Jennings, Phoebe; Garcia-Higuera, Irene; Moreno, Sergio; Jones, Keith T.
- Relation
- ARC.DP1101100418
- Relation
- Molecular Biology of the Cell Vol. 23, Issue 20, p. 3970-3981
- Publisher Link
- http://dx.doi.org/10.1091/mbc.E12-05-0352
- Publisher
- American Society for Cell Biology
- Resource Type
- journal article
- Date
- 2012
- Description
- FZR1 is an anaphase-promoting complex (APC) activator best known for its role in the mitotic cell cycle at M-phase exit, in G1, and in maintaining genome integrity. Previous studies also established that it prevents meiotic resumption, equivalent to the G2/M transition. Here we report that mouse oocytes lacking FZR1 undergo passage through meiosis I that is accelerated by ∼1 h, and this is due to an earlier onset of spindle assembly checkpoint (SAC) satisfaction and APCCDC20 activity. However, loss of FZR1 did not compromise SAC functionality; instead, earlier SAC satisfaction was achieved because the bipolar meiotic spindle was assembled more quickly in the absence of FZR1. This novel regulation of spindle assembly by FZR1 led to premature bivalent attachment to microtubules and loss of kinetochore-bound MAD2. Bivalents, however, were observed to congress poorly, leading to nondisjunction rates of 25%. We conclude that in mouse oocytes FZR1 controls the timing of assembly of the bipolar spindle and in so doing the timing of SAC satisfaction and APCCDC20 activity. This study implicates FZR1 as a major regulator of prometaphase whose activity helps to prevent chromosome nondisjunction.
- Subject
- APC(FZR1); mitotic; oocytes; cell cycle
- Identifier
- http://hdl.handle.net/1959.13/1066863
- Identifier
- uon:18262
- Identifier
- ISSN:1059-1524
- Language
- eng
- Full Text
- Reviewed
- Hits: 9649
- Visitors: 7645
- Downloads: 227
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Publisher version (open access) | 3 MB | Adobe Acrobat PDF | View Details Download |