Proteomics

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Peroxiredoxin 1 protects telomeres from oxidative damage preserving chromosome ends for extension by telomerase


ABSTRACT: With the increase of atmospheric oxygen 2.3 billion years ago, mechanisms evolved to mitigate the toxic effects of oxygen radicals. Telomeres appear particularly susceptible to oxidative damage, which leads to cellular and organismal aging, cancer, cardiac failure and other diseases. Specific mechanisms of telomere protection from oxidative damage and the molecular consequences of the damage have not been described. Here, we identify the antioxidant enzyme peroxiredoxin 1 (PRDX1) enriched in telomeric chromatin in S and G2 phases of the cell cycle during which telomeres become replicated. PRDX1 depletion leads to oxidative damage of telomeric DNA without affecting the bulk of genomic DNA. The oxidized nucleotide 8-oxo-2’deoxyguanosine-5’-triphosphate (8oxodGTP) can be incorporated by telomerase into telomeric repeats but it mediates premature chain termination when incorporated as first G in the telomeric 5’-TTAGGG-3’ sequence. In dependency of the alignment position within the telomerase RNA template, terminus 8oxoG containing DNA substrates also completely block extension by telomerase. We propose two major mechanisms by which PRDX1 counteracts telomere damage and aging. In safeguarding telomeres from oxygen radicals, PRDX1 prevents DNA damage, telomere replication defects and mutations that will perturb recognition of telomeric DNA by shelterin components. In preventing modification of the telomeric DNA substrate and the dNTP pool, PRDX1 preserves telomeres for elongation by telomerase.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Romain Hamelin  

LAB HEAD: Marc Moniatte

PROVIDER: PXD002626 | Pride | 2016-12-07

REPOSITORIES: Pride

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EA_140414_Elite_A01.raw Raw
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Publications

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

Aeby Eric E   Ahmed Wareed W   Redon Sophie S   Simanis Viesturs V   Lingner Joachim J  

Cell reports 20161201 12


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 t  ...[more]

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