Recurrent Micronucleation through Cell Cycle Progression in the Presence of Microtubule Inhibitors

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Author(s)

    • Uno Narumi Uno Narumi
    • Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University|Chromosome Engineering Research Center, Tottori University
    • Uno Katsuhiro Uno Katsuhiro
    • Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University
    • Komoto Shinya Komoto Shinya
    • Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University
    • Kazuki Yasuhiro Kazuki Yasuhiro
    • Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University|Chromosome Engineering Research Center, Tottori University
    • Nanba Eiji Nanba Eiji
    • Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University
    • Oshimura Mitsuo Oshimura Mitsuo
    • Department of Biomedical Science, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University|Chromosome Engineering Research Center, Tottori University

Abstract

Although most cell lines undergo mitotic arrest after prolonged exposure to microtubule inhibitors, some cells subsequently exit this state and become tetraploid. Among these cells, limited numbers of rodent cells are known to undergo multinucleation to generate multiple small independent nuclei, or micronuclei by prolonged colcemid treatment. Micronuclei are thought to be formed when cells shift to a pseudo G1 phase, during which the onset of chromosomal decondensation allows individual chromosomes distributed throughout the cell to serve as sites for the reassembly of nuclear membranes. To better define this process, we used long-term live cell imaging to observe micronucleation induced in mouse A9 cells by treating with the microtubule inhibitor colcemid. Our observations confirm that nuclear envelope formation occurs when mitotic-arrested cells shift to a pseudo G1 phase and adopt a tetraploid state, accompanied by chromosome decondensation. Unexpectedly, only a small number of cells containing large micronuclei were formed. We found that tetraploid micronucleated cells proceeded through an additional cell cycle, shifting to a pseudo G1 phase and forming octoploid micronucleated cells that were smaller and more numerous compared with the tetraploid micronucleated cells. Our data suggest that micronucleation occur when cells shift from mitotic arrest to a pseudo G1 phase, and demonstrate that, rather than being a single event, micronucleation is an inducible recurrent process that leads to the formation of progressively smaller and more numerous micronuclei.

Journal

  • Cell Structure and Function

    Cell Structure and Function 40(1), 51-59, 2015

    Japan Society for Cell Biology

Codes

  • NII Article ID (NAID)
    130004885868
  • NII NACSIS-CAT ID (NCID)
    AA0060007X
  • Text Lang
    ENG
  • ISSN
    0386-7196
  • NDL Article ID
    027281677
  • NDL Call No.
    Z53-V38
  • Data Source
    NDL  J-STAGE 
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