title: New insights into the genetic regulation of homologue disjunction in mammalian oocytes.
abstract: Mammalian oocytes execute a unique meiotic programme involving 2 arrest stages and an unusually protracted preamble to chromosome segregation during the first meiotic division (meiosis I). How mammalian oocytes successfully navigate their exceptional meiotic journey has long been a question of immense interest. Understanding the minutiae of female mammalian meiosis I is not merely of academic interest as 80-90% of human aneuploidy is the consequence of errors arising at this particular stage of oocyte maturation, a stage with a peculiar vulnerability to aging. Recent evidence indicates that oocytes employ many of the same cast of proteins during meiosis I as somatic cells do during mitosis, often to execute similar tasks, but intriguingly, occasionally delegate them to unexpected and unprecedented roles. This is epitomised by the master cell-cycle regulon, the anaphase-promoting complex or cyclosome (APC/C), acting in concert with a critical APC/C-targeted surveillance mechanism, the spindle assembly checkpoint (SAC). Together, the APC/C and the SAC are among the most influential entities overseeing the fidelity of cell-cycle progression and the precision of chromosome segregation. Here I review the current status of pivotal elements underpinning homologue disjunction in mammalian oocytes including spindle assembly, critical biochemical anaphase-initiating events, APC/C activity and SAC signalling along with contemporary findings relevant to progressive oocyte SAC dysfunction as a model for age-related human aneuploidy.
authors.affiliation: Mammalian Oocyte and Embryo Research Laboratory, Department of Cell and Developmental Biology, Division of Biosciences and Institute for Women's Health, University College London, London, UK. h.homer@ucl.ac.uk
authors.forename: H
authors.initials: H
authors.lastname: Homer
mesh_terms: D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D006801:Humans; D008322:Mammals / Q000235:genetics*; D008540:Meiosis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
chemical_list: D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome