Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes.
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. APC(cdh1) 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. APC(cdh1) targeted cdc20 for degradation, but did not target securin or cyclin B1. These were degraded later in MI through APC(cdc20), making cdc20 re-synthesis essential for successful meiotic progression. The switch from APC(cdh1) to APC(cdc20) 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.
Reis
Alexandra
A
Institute for Cell and Molecular Biosciences, The Medical School, Framlington Place, University of Newcastle, Newcastle NE2 4HH, UK.
Madgwick
Suzanne
S
Chang
Heng-Yu
HY
Nabti
Ibtissem
I
Levasseur
Mark
M
Jones
Keith T
KT
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1; D005260:Female; D008540:Meiosis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008856:Microscopy, Fluorescence; D009865:Oocytes / Q000378:metabolism*; D049468:Prometaphase / Q000235:genetics / Q000502:physiology*; D064249:Securin; D013997:Time Factors; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C534700:Ccnb1 protein, mouse; D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome