Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes

Alexandra Reis, Suzanne Madgwick, Heng Yu Chang, Ibtissem Nabti, Mark Levasseur, Keith T. 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.

Original languageEnglish
Pages (from-to)1192-1198
Number of pages7
JournalNature cell biology.
Volume9
Issue number10
DOIs
Publication statusPublished - Oct 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Reis, A., Madgwick, S., Chang, H. Y., Nabti, I., Levasseur, M., & Jones, K. T. (2007). Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes. Nature cell biology., 9(10), 1192-1198. https://doi.org/10.1038/ncb1640