title: Human telomeres maintain their overhang length at senescence.
abstract: Normal human cells in culture enter replicative senescence after a finite number of population doublings. The exact molecular mechanisms triggering the growth arrest are poorly understood. A recent report on the disappearance of the G-rich 3' telomeric overhang in senescent cells led to the hypothesis that loss of the 3' G-rich overhang is the molecular signal that triggers senescence. Here, we describe a quantitative assay to measure the length of the G-rich 3' telomeric overhangs from cultured cells. Using both this assay and the conventional nondenaturing hybridization assay for measuring G-rich overhangs, we show that normal human fibroblasts can maintain their overhangs at senescence. Furthermore, cells do not lose their overhangs when they bypass senescence after the inactivation of p53 and Rb. We thus conclude that a global reduction in overhang length is not the molecular signal that triggers replicative senescence.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9039, USA.
authors.forename: Weihang
authors.initials: W
authors.lastname: Chai
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology; D001681:Biological Assay; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000737:chemistry; D005347:Fibroblasts / Q000166:cytology; D020868:Gene Silencing; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000502:physiology; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000502:physiology; D012261:Ribonucleoproteins / Q000737:chemistry; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D013951:Thymus Hormones / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology
chemical_list: D000952:Antigens, Polyomavirus Transforming; C068651:E6 protein, Human papillomavirus type 16; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D012261:Ribonucleoproteins; D013951:Thymus Hormones; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D004247:DNA
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