Decatenation checkpoint deficiency in stem and progenitor cells

Cancer Cell. 2005 Dec;8(6):479-84. doi: 10.1016/j.ccr.2005.11.004.

Abstract

The decatenation checkpoint normally delays entry into mitosis until chromosomes have been disentangled through the action of topoisomerase II. We have found that the decatenation checkpoint is highly inefficient in mouse embryonic stem cells, mouse neural progenitor cells, and human CD34+ hematopoietic progenitor cells. Checkpoint efficiency increased when embryonic stem cells were induced to differentiate, which suggests that the deficiency is a feature of the undifferentiated state. Embryonic stem cells completed cell division in the presence of entangled chromosomes, which resulted in severe aneuploidy in the daughter cells. The decatenation checkpoint deficiency is likely to increase the rates of chromosome aberrations in progenitor cells, stem cells, and cancer stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Line
  • Chromosome Aberrations
  • Etoposide / pharmacology
  • Genes, cdc*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Mice
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Piperazines / pharmacology
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Time Factors

Substances

  • Piperazines
  • 4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione
  • Etoposide