title: Peroxiredoxin 1 Protects Telomeres from Oxidative Damage and Preserves Telomeric DNA for Extension by Telomerase.
abstract: Oxidative damage of telomeres can promote cancer, cardiac failure, and muscular dystrophy. Specific mechanisms protecting telomeres from oxidative damage have not been described. We analyzed telomeric chromatin composition during the cell cycle and show that the antioxidant enzyme peroxiredoxin 1 (PRDX1) is enriched at telomeres during S phase. Deletion of the PRDX1 gene leads to damage of telomeric DNA upon oxidative stress, revealing a protective function of PRDX1 against oxidative damage at telomeres. We also show that the oxidized nucleotide 8-oxo-2'deoxyguanosine-5'-triphosphate (8oxodGTP) causes premature chain termination when incorporated by telomerase and that some DNA substrates terminating in 8oxoG prevent extension by telomerase. Thus, PRDX1 safeguards telomeres from oxygen radicals to counteract telomere damage and preserve telomeric DNA for elongation by telomerase.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Aeby
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Wareed
authors.initials: W
authors.lastname: Ahmed
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Redon
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Viesturs
authors.initials: V
authors.lastname: Simanis
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: joachim.lingner@epfl.ch.
authors.forename: Joachim
authors.initials: J
authors.lastname: Lingner
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002453:Cell Cycle; D002843:Chromatin / Q000235:genetics; D004247:DNA / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics*; D006801:Humans; D018384:Oxidative Stress / Q000235:genetics*; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000633:toxicity; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*
chemical_list: D002843:Chromatin; D006570:Heterochromatin; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D054464:Peroxiredoxins; D019098:Telomerase; D003849:Deoxyguanosine
keywords: oxidative stress; peroxiredoxin 1; telomerase; telomeres