Peroxiredoxin 1 Protects Telomeres from Oxidative Damage and Preserves Telomeric DNA for Extension by Telomerase

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 (P...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2016-12, Vol.17 (12), p.3107-3114
Main Authors: Aeby, Eric, Ahmed, Wareed, Redon, Sophie, Simanis, Viesturs, Lingner, Joachim
Format: Article
Language:English
Subjects:
Cell Cycle
Chromatin - genetics
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - metabolism
DNA - genetics
DNA Damage - genetics
Heterochromatin - genetics
Humans
oxidative stress
Oxidative Stress - genetics
peroxiredoxin 1
Peroxiredoxins - genetics
Peroxiredoxins - metabolism
Reactive Oxygen Species - toxicity
telomerase
Telomerase - genetics
Telomere - genetics
telomeres
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Summary: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. [Display omitted] •The antioxidant enzyme PRDX1 associates with telomeric chromatin•PRDX1 protects telomeres from oxidative damage•Oxidized telomeric DNA cannot be extended by telomerase Aeby et al. analyze the protein composition of telomeres during the cell cycle. The antioxidant enzyme PRDX1 associates with telomeres during S and G2 phases of the cell cycle. Deletion studies reveal that PRDX1 protects telomeres from acute oxidative damage. Oxidized telomeric DNA cannot be extended by telomerase.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2016.11.071