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

Publication date: 20 December 2016
Source:Cell Reports, Volume 17, Issue 12
Author(s): Eric Aeby, Wareed Ahmed, Sophie Redon, Viesturs Simanis, Joachim Lingner
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.

Graphical abstract

Teaser

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.


http://ift.tt/2hK3JSK