title: The meiosis I-to-meiosis II transition in mouse oocytes requires separase activity.
abstract: Faithful segregation of homologous chromosomes during the first meiotic division is essential for further embryo development. The question at issue is whether the same mechanisms ensuring correct separation of sister chromatids in mitosis are at work during the first meiotic division. In mitosis, sister chromatids are linked by a cohesin complex holding them together until their disjunction at anaphase. Their disjunction is mediated by Separase, which cleaves the cohesin. The activation of Separase requires prior degradation of its associated inhibitor, called securin. Securin is a target of the APC/C (Anaphase Promoting Complex/Cyclosome), a cell cycle-regulated ubiquitin ligase that ubiquitinates securin at the metaphase-to-anaphase transition and thereby targets it for degradation by the 26S proteasome. After securin degradation, Separase cleaves the cohesins and triggers chromatid separation, a prerequisite for anaphase. In yeast and worms, the segregation of homologous chromosomes in meiosis I depends on the APC/C and Separase activity. Yet, it is unclear if Separase is required for the first meiotic division in vertebrates because APC/C activity is thought to be dispensable in frog oocytes. We therefore investigated if Separase activity is required for correct chromosome segregation in meiosis I in mouse oocytes.
authors.affiliation: Division Méiotiques, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, 75252 Paris, cedex 05, France.
authors.forename: M Emilie
authors.initials: ME
authors.lastname: Terret
authors.forename: Katja
authors.initials: K
authors.lastname: Wassmann
authors.forename: Irene
authors.initials: I
authors.lastname: Waizenegger
authors.forename: Bernard
authors.initials: B
authors.lastname: Maro
authors.forename: Jan Michael
authors.initials: JM
authors.lastname: Peters
authors.forename: Marie Hélène
authors.initials: MH
authors.lastname: Verlhac
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism* / Q000502:physiology; D005260:Female; D007976:Leupeptins / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008845:Microinjections; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D064247:Separase
chemical_list: D018797:Cell Cycle Proteins; D007976:Leupeptins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C465863:Rec8 protein, mouse; D010450:Endopeptidases; D010447:Peptide Hydrolases; D064247:Separase; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde