4.7 Article

The roles of kinetochore of micronucleus in mitosis of HeLa cells: a live cell imaging study

Journal

CANCER CELL INTERNATIONAL
Volume 19, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12935-019-0917-8

Keywords

Micronucleus; Kinetochore; Lagging chromosome; Chromosome fragment; Mitosis; Live cell imaging

Categories

Funding

  1. Key Project of Natural Science Foundation from Department of Education, Anhui Provincial [03087060]
  2. Key Natural Science Foundation from Department of Education, Anhui Provincial [2013A110]
  3. Foundation of Anhui Provincial Key Disciplines of Biology [2014JXJS002, 2014SKQJ016]
  4. Anhui Agricultural University Foundation for Stability and Introduction of Talent
  5. Key Project of Natural Science Foundation of the Anhui Provincial Education Department

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Background Micronuclei (MNi) are extensively used to evaluate genotoxic effects and chromosome instability. However, the roles of kinetochore of MN in mitosis have not been completely addressed. Methods The HeLa CENP B-GFP H2B-mCherry cells are applied to address these questions via the long-term live-cell imaging. In the cells, the kinetochore-positive micronucleus (K+MN) contained CENP B-GFP, while the kinetochore-negative micronucleus (K-MN) did not. Results K-MN-bearing cells produced much more chromosome fragments than did MN-free cells. Most of the chromosome fragments eventually merged into K-MNi. K+MN-bearing cells yielded more kinetochore-positive lagging chromosomes (K+LCs) and K+MNi than MN-free cells did. The results suggested the differences in the fates of K+MNi and K-MNi in mitosis. The cycle of K-MN -> Chromosome fragment -> K-MN may occur in generations of K-MN-bearing cells, while part of K+MNi might reincorporate into the main nucleus. The K+MN-bearing cells prolonged significantly duration of mitosis compared with MN-free cells. The presence of micronuclei, regardless of K-MN and K+MN, enhanced apoptosis cell death. And K+MN-bearing cells were inclined to apoptosis more than K-MN-bearing cells. The results suggested differences in fates between K-MN-bearing and K+MN-bearing cells. Conclusions Kinetochore determined the fates of micronuclei. Kinetochore in micronuclei indirectly prolonged the duration of mitosis. Kinetochore enhanced cytotoxicity of micronuclei. Our data are direct evidences showing the roles of kinetochore of micronucleus in mitosis of HeLa cells.

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