title: Transient ALT activation protects human primary cells from chromosome instability induced by low chronic oxidative stress.
abstract: Cells are often subjected to the effect of reactive oxygen species (ROS) as a result of both intracellular metabolism and exposure to exogenous factors. ROS-dependent oxidative stress can induce 8-oxodG within the GGG triplet found in the G-rich human telomeric sequence (TTAGGG), making telomeres highly susceptible to ROS-induced oxidative damage. Telomeres are nucleoprotein complexes that protect the ends of linear chromosomes and their dysfunction is believed to affect a wide range of cellular and/or organismal processes. Acute oxidative stress was shown to affect telomere integrity, but how prolonged low level oxidative stress, which may be more physiologically relevant, affects telomeres is still poorly investigated. Here, we explored this issue by chronically exposing human primary fibroblasts to a low dose of hydrogen peroxide. We observed fluctuating changes in telomere length and fluctuations in the rates of chromosome instability phenotypes, such that when telomeres shortened, chromosome instability increased and when telomeres lengthened, chromosome instability decreased. We found that telomere length fluctuation is associated with transient activation of an alternative lengthening of telomere (ALT) pathway, but found no evidence of cell death, impaired proliferation, or cell cycle arrest, suggesting that ALT activation may prevent oxidative damage from reaching levels that threaten cell survival.
authors.affiliation: Department of Science, University Roma Tre, V. le G. Marconi, 446, 00146, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Coluzzi
authors.affiliation: Department of Science, University Roma Tre, V. le G. Marconi, 446, 00146, Rome, Italy.|Department of Biological Sciences, Virginia Tech, Blacksburg, VA, 24061, USA.
authors.forename: Rossella
authors.initials: R
authors.lastname: Buonsante
authors.affiliation: Department of Science, University Roma Tre, V. le G. Marconi, 446, 00146, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, 24061, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Asmar
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, 24061, USA.
authors.forename: Kelley L
authors.initials: KL
authors.lastname: Miller
authors.affiliation: Department of Biological Sciences, Virginia Tech, Blacksburg, VA, 24061, USA.|Biocomplexity Institute, Virginia Tech, 1015 Life Science Circle, Blacksburg, VA, 24061, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cimini
authors.affiliation: Department of Science, University Roma Tre, V. le G. Marconi, 446, 00146, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Sgura
mesh_terms: D002470:Cell Survival; D016922:Cellular Senescence / Q000187:drug effects; D043171:Chromosomal Instability / Q000187:drug effects*; D048749:Cytokinesis / Q000187:drug effects; D005333:Fetus; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017404:In Situ Hybridization, Fluorescence; D018386:Kinetochores / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis / Q000187:drug effects; D018384:Oxidative Stress; D061251:Primary Cell Culture; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D059505:Telomere Homeostasis; D059008:Time-Lapse Imaging
chemical_list: D006861:Hydrogen Peroxide