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MCAK regulates chromosome alignment but is not necessary for preventing aneuploidy in mouse oocyte meiosis I

Illingworth, C; Pirmadjid, N; Serhal, P; Howe, K; FitzHarris, G; (2010) MCAK regulates chromosome alignment but is not necessary for preventing aneuploidy in mouse oocyte meiosis I. DEVELOPMENT , 137 (13) 2133 - 2138. 10.1242/dev.048306.

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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.

Type: Article
Title: MCAK regulates chromosome alignment but is not necessary for preventing aneuploidy in mouse oocyte meiosis I
DOI: 10.1242/dev.048306
Keywords: MCAK (KIF2C), Aneuploidy, Mammalian oocyte, Spindle, Mouse, CENTROMERE-ASSOCIATED KINESIN, SMALL-MOLECULE INHIBITOR, MAMMALIAN TISSUE-CELLS, MITOTIC CENTROMERE, AURORA-B, MICROTUBULE DYNAMICS, SPINDLE, MITOSIS, PROTEIN, AGE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/356070
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