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

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

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It is widely accepted that mammalian cells enter the next G1-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.

Authors

Charlie Mantel

Indiana University School of Medicine; Indianapolis, IN

Ying Guo

Indiana University School of Medicine; Indianapolis, IN

Man Ryul Lee

Hanyang University College of Medicine; Seoul, South Korea

Myung-Kwan Han

Chonbuk National University Medical School; Jeonju, South Korea

Sara Rhorabough

Indiana University School of Medicine; Indianapolis, IN

Kye-Seong Kim

Hanyang University College of Medicine; Seoul, South Korea

Hal E. Broxmeyer

Indiana University School of Medicine; Indianapolis, IN

Purchase article for $19

Subscribe to this journal for $129/year