title: Enforced telomere elongation increases the sensitivity of human tumour cells to ionizing radiation.
abstract: More than 85% of all human cancers possess the ability to maintain chromosome ends, or telomeres, by virtue of telomerase activity. Loss of functional telomeres is incompatible with survival, and telomerase inhibition has been established in several model systems to be a tractable target for cancer therapy. As human tumour cells typically maintain short equilibrium telomere lengths, we wondered if enforced telomere elongation would positively or negatively impact cell survival. We found that telomere elongation beyond a certain length significantly decreased cell clonogenic survival after gamma irradiation. Susceptibility to irradiation was dosage-dependent and increased at telomere lengths exceeding 17kbp despite the fact that all chromosome ends retained telomeric DNA. These data suggest that an optimal telomere length may promote human cancer cell survival in the presence of genotoxic stress.
authors.affiliation: Wellcome Trust Centre for Cell Biology and Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Mayfield Road, EH9 3JR Edinburgh, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fairlie
authors.affiliation: Wellcome Trust Centre for Cell Biology and Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Mayfield Road, EH9 3JR Edinburgh, UK; Institute for Research in Immunology and Cancer, Department of Medicine, University of Montreal, 2950 chemin de Polytechnique, Montreal, Canada H3T 1J4. Electronic address: lea.harrington@umontreal.ca.
authors.forename: Lea
authors.initials: L
authors.lastname: Harrington
mesh_terms: D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D005720:Gamma Rays; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis; D014407:Tumor Cells, Cultured
keywords: DNA damage; Gamma irradiation; Human tumour cells; Telomerase; Telomeres