Oxidative guanine base damage regulates human telomerase activity
Open accessAbstract
Changes in telomere length are associated with degenerative diseases and cancer. Oxidative stress and DNA damage have been linked to both positive and negative alterations in telomere length and integrity. Here we examined how the common oxidative lesion 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG) regulates telomere elongation by human telomerase. When 8-oxoG is present in the dNTP pool as 8-oxodGTP, telomerase utilization of the oxidized nucleotide during telomere extension is mutagenic and terminates further elongation. Depletion of MTH1, the enzyme that removes oxidized dNTPs, increases telomere dysfunction and cell death in telomerase-positive cancer cells with shortened telomeres. In contrast, a preexisting 8-oxoG within the telomeric DNA sequence promotes telomerase activity by destabilizing the G-quadruplex DNA structure. We show that the mechanism by which 8-oxoG arises in telomeres, either by insertion of oxidized nucleotides or by direct reaction with free radicals, dictates whether telomerase is inhibited or stimulated and thereby mediates the biological outcome.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Oxidative stress induces tDD without telomere shortening and accelerates telomere shortening by inhibiting telomerase and disrupting recognition by telomere-binding proteins, contributing to uncapping.
“Oxidative stress reportedly both induces tDD without telomere shortening and accelerates telomere shortening23–26 by inhibiting telomerase27 and disrupting the recognition by telomere-binding proteins, which contributes to telomere uncapping22,28.”
From Telomere dysfunction in ageing and age-related diseases (2022) · cites this paper as [27]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 65 · Cited by 182
- Authors
- Fouquerel, E., Lormand, J., Bose, A., Lee, H.-T., Kim, G. S., Li, J., Sobol, R. W., Freudenthal, B. D., Myong, S., & Opresko, P. L.
- Affiliations
- University of Pittsburgh (US)
- Johns Hopkins University (US)
- University of Illinois Urbana-Champaign (US)
- University of South Alabama (US)
- University of Kansas Medical Center (US)
- Corresponding author
- Opresko, Patricia L
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2016-11-07
- Volume
- 23
- Issue
- 12
- Pages
- 1092-1100
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC5140714
- OpenAlex
- W2554833173
- Cited by
- 182
- References
- 65
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 19 · 2023: 12 · 2022: 22 · 2021: 20 · 2020: 30 · 2019: 18 · 2018: 17 · 2017: 18 · 2016: 1
- FWCI
- 14.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Cancer Institute, University of Pittsburgh
- National Institute on Aging (R21AG045545)
- National Cancer Institute (R01CA148629, R01CA207342, P30CA047904)
- National Institute of General Medical Sciences (R01GM115631, DP2GM105453)
- National Institute of Environmental Health Sciences (R21ES025606, R00ES024431, R01ES022944)
- Topics
- Health Sciences › Medicine › Physiology › 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 › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- oxidative DNA damage, human telomerase, telomere elongation, G-quadruplex, MTH1, mutagenesis, telomere dysfunction, oxidative stress, telomere length, cancer cells, free radicals
- MeSH terms
- Base Sequence, Cell Line, Deoxyguanine Nucleotides, DNA, DNA Damage, Enzyme Activation, Humans, Mutagens, Oxidation-Reduction, Telomere, Cell Death, Oxidative Stress, DNA Adducts, Telomerase, Cell Line, Tumor, G-Quadruplexes, Telomere Shortening
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
