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

The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint
The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint
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.
0022-4251
521-530
Lane, SIR
8e80111f-5012-4950-a228-dfb8fb9df52d
Chang, HY
10ef9357-7f7b-432f-86d3-33c03f348980
Jennings, PC
fba9ff1d-c590-4715-b2d9-174bcb4c1678
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Lane, SIR
8e80111f-5012-4950-a228-dfb8fb9df52d
Chang, HY
10ef9357-7f7b-432f-86d3-33c03f348980
Jennings, PC
fba9ff1d-c590-4715-b2d9-174bcb4c1678
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4

Lane, SIR, Chang, HY, Jennings, PC and Jones, KT (2010) The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. Reproduction, 140 (4), 521-530. (doi:10.1530/REP-10-0223). (PMID:20660090)

Record type: Article

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.

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More information

e-pub ahead of print date: 21 July 2010
Published date: 1 October 2010
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 349667
URI: http://eprints.soton.ac.uk/id/eprint/349667
ISSN: 0022-4251
PURE UUID: 470adb7a-9d2b-4b5f-a444-c9503f4124fd
ORCID for SIR Lane: ORCID iD orcid.org/0000-0002-8155-0981
ORCID for KT Jones: ORCID iD orcid.org/0000-0002-0294-0851

Catalogue record

Date deposited: 07 Mar 2013 16:30
Last modified: 26 Nov 2019 01:37

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