Letter abstract
Nature Cell Biology 9, 1192 - 1198 (2007)
Published online: 23 September 2007 | doi:10.1038/ncb1640
Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes
Alexandra Reis1, Suzanne Madgwick1, Heng-Yu Chang1, Ibtissem Nabti1, Mark Levasseur1 & Keith T. Jones1
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.
- Institute for Cell and Molecular Biosciences, The Medical School, Framlington Place, University of Newcastle, Newcastle NE2 4HH, UK
Correspondence to: Keith T. Jones1 e-mail: k.t.jones@ncl.ac.uk
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
APC cdh1 activity in mouse oocytes prevents entry into the first meiotic divisionNature Cell Biology Brief Communication
Securin regulates entry into M-phase by modulating the stability of cyclin BNature Cell Biology Letter (01 Apr 2008)
Dose-dependent effects of stable cyclin B1 on progression through mitosis in human cellsThe EMBO Journal Article (21 Jun 2006)
See all 29 matches for Research