title: Erosion of the telomeric single-strand overhang at replicative senescence.
abstract: Cultured primary human cells inevitably enter a state of replicative senescence for which the specific molecular trigger is unknown. We show that the single-strand telomeric overhang, a key component of telomere structure, is eroded at senescence. Expression of telomerase prevents overhang loss, suggesting that this enzyme prevents senescence by maintaining proper telomere structure. In contrast, progressive overhang loss occurs in cells that avoid senescence through the inactivation of p53 and Rb, indicating that overhang erosion is the result of continuous cell division and not a consequence of senescence. We thus provide evidence for a specific molecular alteration in telomere structure at senescence and suggest that this change, rather than overall telomere length, serves to trigger this state.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Stewart
authors.forename: Ittai
authors.initials: I
authors.lastname: Ben-Porath
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: O'Connor
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weinberg
mesh_terms: D000957:Antigens, Viral, Tumor / Q000378:metabolism; D015139:Blotting, Southern; D002455:Cell Division; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003720:Densitometry; D005347:Fibroblasts / Q000378:metabolism; D005821:Genetic Techniques; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism; D016615:Telomere / Q000378:metabolism* / Q000502:physiology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000957:Antigens, Viral, Tumor; D011500:Protein Synthesis Inhibitors; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53