The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint

Simon I R Lane, Heng Yu Chang, Phoebe C. Jennings, Keith T. Jones

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Previous studies have established that when maturing mouse oocytes are continuously incubated with the Aurora inhibitor ZM447439, meiotic maturation is blocked. In this study, we observe that by altering the time of addition of the inhibitor, oocyte maturation can actually be accelerated by 1 h as measured by the timing of polar body extrusion. ZM447439 also had the ability to overcome a spindle assembly checkpoint (SAC) arrest caused by nocodazole and so rescue polar body extrusion. Consistent with the ability of the SAC to inhibit cyclin B1 degradation by blocking activation of the anaphase-promoting complex, we could also observe a rescue in cyclin B1 degradation when ZM447439 was added to nocodazole-treated oocytes. The acceleration of the first meiotic division by ZM447439, which has not been achieved previously, and its effects on the SAC are all consistent with the proposed mitotic role of Aurora B in activating the SAC. We hypothesize that Aurora kinase activity controls the SAC in meiosis I, despite differences to the mitotic cell cycle division in spindle architecture brought about by the meiotic mono-orientation of sister kinetochores.

Original languageEnglish
Pages (from-to)521-530
Number of pages10
JournalReproduction
Volume140
Issue number4
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

Fingerprint

Aurora Kinases
M Phase Cell Cycle Checkpoints
Meiosis
Oocytes
Polar Bodies
Cyclin B1
Nocodazole
Anaphase-Promoting Complex-Cyclosome
Kinetochores
Cell Cycle
4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine
  • Embryology
  • Endocrinology
  • Cell Biology

Cite this

The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. / Lane, Simon I R; Chang, Heng Yu; Jennings, Phoebe C.; Jones, Keith T.

In: Reproduction, Vol. 140, No. 4, 10.2010, p. 521-530.

Research output: Contribution to journalArticle

Lane, Simon I R ; Chang, Heng Yu ; Jennings, Phoebe C. ; Jones, Keith T. / The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. In: Reproduction. 2010 ; Vol. 140, No. 4. pp. 521-530.
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