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Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes

Lookup NU author(s): Dr Alexandra Reis, Dr Suzanne Madgwick, Ibtissem Nabti, Dr Mark Levasseur, Professor Keith Jones

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Abstract

The first female meiotic division (meiosis I, MI) is uniquely prone to chromosome segregation errors through non-disjunction, resulting in trisomies and early pregnancy loss. Here, we show a fundamental difference in the control of mammalian meiosis that may underlie such susceptibility. It involves a reversal in the well-established timing of activation of the anaphase-promoting complex (APC) by its co-activators cdc20 and cdh1. APCcdh1 was active first, during prometaphase I, and was needed in order to allow homologue congression, as loss of cdh1 speeded up MI, leading to premature chromosome segregation and a non-disjunction phenotype. APCcdh1 targeted cdc20 for degradation, but did not target securin or cyclin B1. These were degraded later in MI through APCcdc20, making cdc20 re-synthesis essential for successful meiotic progression. The switch from APCcdh1 to APCcdc20 activity was controlled by increasing CDK1 and cdh1 loss. These findings demonstrate a fundamentally different mechanism of control for the first meiotic division in mammalian oocytes that is not observed in meioses of other species.


Publication metadata

Author(s): Reis A, Madgwick S, Chang H-Y, Nabti I, Levasseur M, Jones KT

Publication type: Article

Publication status: Published

Journal: Nature Cell Biology

Year: 2007

Volume: 9

Issue: 10

Pages: 1192-1198

ISSN (print): 1465-7392

ISSN (electronic): 1476-4679

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ncb1640

DOI: 10.1038/ncb1640

PubMed id: 17891138


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Funding

Funder referenceFunder name
Wellcome Trust
075744Wellcome Trust

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