Aeby Eric, Ahmed Wareed, Redon Sophie, Simanis Viesturs, Lingner Joachim
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Cell Rep. 2016 Dec 20;17(12):3107-3114. doi: 10.1016/j.celrep.2016.11.071.
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.
端粒的氧化损伤可促进癌症、心力衰竭和肌肉萎缩症。尚未描述保护端粒免受氧化损伤的具体机制。我们分析了细胞周期中端粒染色质的组成，发现抗氧化酶过氧化物还原酶1（PRDX1）在S期富集于端粒。PRDX1基因的缺失导致氧化应激下的端粒DNA损伤，揭示了PRDX1对端粒氧化损伤的保护作用。我们还表明，氧化核苷酸8-氧代-2'-脱氧鸟苷-5'-三磷酸（8oxodGTP）在被端粒酶掺入时会导致链过早终止，并且一些以8oxoG结尾的DNA底物会阻止端粒酶的延伸。因此，PRDX1保护端粒免受氧自由基的影响，以对抗端粒损伤并保留端粒DNA以供端粒酶延长。
