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

Lookup NU author(s): Professor Keith Jones

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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. Reproduction (2010) 140 521-530

Publication metadata

Author(s): Lane SIR, Chang HY, Jennings PC, Jones KT

Publication type: Article

Publication status: Published

Journal: Reproduction

Year: 2010

Volume: 140

Issue: 4

Pages: 521-530

Print publication date: 01/10/2010

ISSN (print): 1470-1626

ISSN (electronic): 1741-7899

Publisher: BioScientifica Ltd.

URL: http://dx.doi.org/10.1530/REP-10-0223

DOI: 10.1530/REP-10-0223

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