Cells enter a unique intermediate 4N stage, not 4N-G1, after aborted mitosis

Charlie Mantel, Ying Guo, Ryul Lee Man, Kwan Han Myung, Sara Rohrabough, Seong Kim Kye, Hal E. Broxmeyer

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

It is widely accepted that mammalian cells enter the next G 1-phase (G1) with 4N DNA after slippage from prolonged drug-induced mitotic block caused by activation of the transient spindle checkpoint. Understanding cell fate after mitotic slippage (MS) has significant clinical importance. The conclusion the MS cells enter 4N-G1 is based on morphology and mitotic cyclin destruction. Definitive biochemical evidence for G1 is scarce or unconvincing, in part because of methods of protein extraction required for immunoblot analysis that cannot take into account the cell cycle heterogeneity of cell cultures. We used single-cell-intracellular-flow-cytometric analysis to further define important factors determining cell fate after MS. Results from human and mouse embryonic stem cells (ESC) that reenter polyploid cell cycles are compared to human somatic cells that die after MS. We conclude that phosphorylation status of pRb, p53, CDK1 and especially cyclin B1 levels are important for cell fate decision in MS cells, which occur in a unique, intervening, non-G1, tetraploid subphase.

Original languageEnglish (US)
Pages (from-to)484-492
Number of pages9
JournalCell Cycle
Volume7
Issue number4
DOIs
StatePublished - Feb 15 2008

Keywords

  • Cell cycle
  • Cell cycle checkpoint
  • Embryonic stem cell
  • Flow cytometry
  • Mitotic exit
  • Polyploidy

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

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  • Cite this

    Mantel, C., Guo, Y., Man, R. L., Myung, K. H., Rohrabough, S., Kye, S. K., & Broxmeyer, H. E. (2008). Cells enter a unique intermediate 4N stage, not 4N-G1, after aborted mitosis. Cell Cycle, 7(4), 484-492. https://doi.org/10.4161/cc.7.4.5316