Cited by 290Telomeres, Telomerase, and SenescenceDNA and Nucleic Acid ChemistryDNA Repair Mechanisms

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Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2

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Opresko, P. L.·2005·Nucleic Acids Research

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Abstract

The ends of linear chromosomes are capped by protein-DNA complexes termed telomeres. Telomere repeat binding factors 1 and 2 (TRF1 and TRF2) bind specifically to duplex telomeric DNA and are critical components of functional telomeres. Consequences of telomere dysfunction include genomic instability, cellular apoptosis or senescence and organismal aging. Mild oxidative stress induces increased erosion and loss of telomeric DNA in human fibroblasts. We performed binding assays to determine whether oxidative DNA damage in telomeric DNA alters the binding activity of TRF1 and TRF2 proteins. Here, we report that a single 8-oxo-guanine lesion in a defined telomeric substrate reduced the percentage of bound TRF1 and TRF2 proteins by at least 50%, compared with undamaged telomeric DNA. More dramatic effects on TRF1 and TRF2 binding were observed with multiple 8-oxo-guanine lesions in the tandem telomeric repeats. Binding was likewise disrupted when certain intermediates of base excision repair were present within the telomeric tract, namely abasic sites or single nucleotide gaps. These studies indicate that oxidative DNA damage may exert deleterious effects on telomeres by disrupting the association of telomere-maintenance proteins TRF1 and TRF2.

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Authors: Opresko, P. L.
Affiliations: National Institutes of Health (US)
Corresponding author: Opresko, P. L.
ORCID: Opresko, P. L.
Venue: Nucleic Acids Research
Publisher: Oxford University Press (OUP)
Published: 2005-02-23
Volume: 33
Issue: 4
Pages: 1230-1239
ISSN: 0305-1048 (ISSN-L)
1362-4962
DOI: 10.1093/nar/gki273
PMC: PMC549571
OpenAlex: W2098312065
Cited by: 289
References: 40
Citations by year: 2026: 10 · 2025: 15 · 2024: 10 · 2023: 17 · 2022: 19 · 2021: 20 · 2020: 23 · 2019: 18 · 2018: 15 · 2017: 14 · 2016: 20 · 2015: 20 · 2014: 17 · 2013: 14 · 2012: 6
FWCI: 4.61
Type: journal article
Language: en
Open access: gold
doi.org
Licence: other-oa
Locations: Nucleic Acids Research (publishedVersion, other-oa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords: telomeres, TRF1, TRF2, oxidative DNA damage, 8-oxoguanine, telomeric DNA binding, base excision repair, abasic sites, telomere dysfunction, telomere shortening
MeSH terms: DNA, DNA Damage, Guanine, Humans, Telomere, Oxidative Stress, Telomeric Repeat Binding Protein 1, Telomeric Repeat Binding Protein 2

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Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2

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