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Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes

Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes
Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes
The spindle assembly checkpoint (SAC) prevents aneuploidy by coupling anaphase onset, through anaphase-promoting complex (APC) activation, with chromosome attachment to spindle microtubules. Here, we examine APC activity in oocytes, noted for their susceptibility to chromosome mis-segregation during the first meiotic division (MI). We find that MI oocytes only contain sub-maximal APC activity, measured through cyclin B1–GFP degradation, because inhibition of SAC proteins when the APC is normally fully active increases cyclin B1 degradation twofold and reduces the length of this division by 2?h. In addition, inhibiting the SAC component Mps1 only when the APC is already active increases aneuploidy rates in the resulting egg by up to 30%. We therefore establish that the activities of SAC proteins and the APC co-exist in oocytes, and such concurrence has a vital role in reducing aneuploidy rates by extending MI, probably by allowing time for numerous erroneous microtubule attachments to be corrected
3444
Lane, SIR
8e80111f-5012-4950-a228-dfb8fb9df52d
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4
Lane, SIR
8e80111f-5012-4950-a228-dfb8fb9df52d
Jones, KT
73e8e2b5-cd67-4691-b1a9-4e7bc9066af4

Lane, SIR and Jones, KT (2014) Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes. Nature Communications, 5, 3444. (doi:10.1038/ncomms4444).

Record type: Article

Abstract

The spindle assembly checkpoint (SAC) prevents aneuploidy by coupling anaphase onset, through anaphase-promoting complex (APC) activation, with chromosome attachment to spindle microtubules. Here, we examine APC activity in oocytes, noted for their susceptibility to chromosome mis-segregation during the first meiotic division (MI). We find that MI oocytes only contain sub-maximal APC activity, measured through cyclin B1–GFP degradation, because inhibition of SAC proteins when the APC is normally fully active increases cyclin B1 degradation twofold and reduces the length of this division by 2?h. In addition, inhibiting the SAC component Mps1 only when the APC is already active increases aneuploidy rates in the resulting egg by up to 30%. We therefore establish that the activities of SAC proteins and the APC co-exist in oocytes, and such concurrence has a vital role in reducing aneuploidy rates by extending MI, probably by allowing time for numerous erroneous microtubule attachments to be corrected

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More information

Accepted/In Press date: 12 February 2014
e-pub ahead of print date: 18 March 2014
Published date: 2014
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 363234
URI: http://eprints.soton.ac.uk/id/eprint/363234
PURE UUID: cd4f8a41-c45a-4e2e-b0dd-a14856c53d3d
ORCID for SIR Lane: ORCID iD orcid.org/0000-0002-8155-0981
ORCID for KT Jones: ORCID iD orcid.org/0000-0002-0294-0851

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Date deposited: 21 Mar 2014 14:38
Last modified: 29 Oct 2019 01:39

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Author: SIR Lane ORCID iD
Author: KT Jones ORCID iD

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