title: A three-state model of telomere control over human proliferative boundaries.
abstract: 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.
authors.affiliation: The Salk Institute for Biological Studies, Molecular and Cell Biology Laboratory, 10010 North Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Cesare
authors.forename: Jan
authors.initials: J
authors.lastname: Karlseder
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D013312:Stress, Physiological; D016615:Telomere / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology