title: Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes.
abstract: The spindle assembly checkpoint (SAC) prevents aneuploidy by coupling anaphase onset, through anaphase-promoting complex (APC) activation, with chromosome attachment to spindle microtubules. Here, we examine APC activity in oocytes, noted for their susceptibility to chromosome mis-segregation during the first meiotic division (MI). We find that MI oocytes only contain sub-maximal APC activity, measured through cyclin B1-GFP degradation, because inhibition of SAC proteins when the APC is normally fully active increases cyclin B1 degradation twofold and reduces the length of this division by 2 h. In addition, inhibiting the SAC component Mps1 only when the APC is already active increases aneuploidy rates in the resulting egg by up to 30%. We therefore establish that the activities of SAC proteins and the APC co-exist in oocytes, and such concurrence has a vital role in reducing aneuploidy rates by extending MI, probably by allowing time for numerous erroneous microtubule attachments to be corrected.
authors.affiliation: 1] Centre for Biological Sciences, Faculty and Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK [2] School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Simon I R
authors.initials: SI
authors.lastname: Lane
authors.affiliation: 1] Centre for Biological Sciences, Faculty and Natural and Environmental Sciences, University of Southampton, Southampton SO17 1BJ, UK [2] School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan, New South Wales 2308, Australia.
authors.forename: Keith T
authors.initials: KT
authors.lastname: Jones
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D020090:Chromosome Segregation; D056744:Cyclin B1 / Q000378:metabolism; D005260:Female; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D056744:Cyclin B1; D064173:Anaphase-Promoting Complex-Cyclosome; C441620:Ttk protein, mouse; D017346:Protein Serine-Threonine Kinases