A three-state model of telomere control over human proliferative boundaries

Curr Opin Cell Biol. 2012 Dec;24(6):731-8. doi: 10.1016/j.ceb.2012.08.007. Epub 2012 Sep 2.


Intrinsic limits on cellular proliferation in human somatic tissue serves as a tumor suppressor mechanism by restricting cell growth in aged cells with accrued pre-cancerous mutations. This is accompanied by the potential cost of restricting regenerative capacity and contributing to cellular and organismal aging. Emerging data support a model where telomere erosion controls proliferative boundaries through the progressive change of telomere structure from a protected state, through two distinct states of telomere deprotection. In this model telomeres facilitate a controlled permanent cell cycle arrest with a stable diploid genome during differentiation and may serve as an epigenetic sensor of general stress in DNA metabolism processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation*
  • Cellular Senescence / genetics*
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Models, Biological*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Stress, Physiological
  • Telomere / genetics*
  • Telomere / metabolism*
  • Telomere / pathology