title: MCAK regulates chromosome alignment but is not necessary for preventing aneuploidy in mouse oocyte meiosis I.
abstract: Errors in chromosome segregation in mammalian oocytes lead to aneuploid eggs that are developmentally compromised. In mitotic cells, mitotic centromere associated kinesin (MCAK; KIF2C) prevents chromosome segregation errors by detaching incorrect microtubule-kinetochore interactions. Here, we examine whether MCAK is involved in spindle function in mouse oocyte meiosis I, and whether MCAK is necessary to prevent chromosome segregation errors. We find that MCAK is recruited to centromeres, kinetochores and chromosome arms in mid-meiosis I, and that MCAK depletion, or inhibition using a dominant-negative construct, causes chromosome misalignment. However, the majority of oocytes complete meiosis I and the resulting eggs retain the correct number of chromosomes. Moreover, MCAK-depleted oocytes can recover from mono-orientation of homologous kinetochores in mid-meiosis I to segregate chromosomes correctly. Thus, MCAK contributes to chromosome alignment in meiosis I, but is not necessary for preventing chromosome segregation errors. Although other correction mechanisms may function in mammalian meiosis I, we speculate that late establishment of kinetochore microtubules in oocytes reduces the likelihood of incorrect microtubule-kinetochore interactions, bypassing the requirement for error correction.
authors.affiliation: University College London Institute for Women's Health, 86-96 Chenies Mews, London WC1E6HX, UK.
authors.forename: Crista
authors.initials: C
authors.lastname: Illingworth
authors.forename: Negar
authors.initials: N
authors.lastname: Pirmadjid
authors.forename: Paul
authors.initials: P
authors.lastname: Serhal
authors.forename: Katie
authors.initials: K
authors.lastname: Howe
authors.forename: Greg
authors.initials: G
authors.lastname: Fitzharris
mesh_terms: D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C550146:Kif2c protein, mouse; D016547:Kinesins