The first female meiotic division (meiosis I, MI) is uniquely prone to chromosome segregation errors through non-disjunction, resulting in trisomies and early pregnancy loss¹. 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)²,³ 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.
Nature Cell Biology Vol. 9, Issue 10, p. 1192-1198