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

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

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The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA.


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.

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