ArticleNature2015
Uncovering the polymerase-induced cytotoxicity of an oxidized nucleotide.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 159 citations in OpenAlex.
- The Enzymatic Mechanism of OAS: How Metal Ions and Quantum Effects Help Activate Innate Immunity.ACS omega · 2026Article
- A Comparative Study for the Incorporation of 8-oxo-dATP in DNA by Human DNA Polymerases.International journal of molecular sciences · 2026Article
- Review
- Unraveling the Vicious Cycle: Oxidative Stress and Neurotoxicity in Neurodegenerative Diseases.FASEB bioAdvances · 2025Review
- Oxidative Stress and DNA Damage at Telomeres.Cold Spring Harbor perspectives in biology · 2025Review
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- Role of Oxidative Stress in the Occurrence, Development, and Treatment of Breast Cancer.Antioxidants (Basel, Switzerland) · 2025Review
- TORC2 inhibition triggers yeast chromosome fragmentation through misregulated Base Excision Repair of clustered oxidation events.Nature communications · 2024Article
- Effects of the Y432S Cancer-Associated Variant on the Reaction Mechanism of Human DNA Polymerase κ.Journal of chemical information and modeling · 2024Article
- Biochemical and structural characterization of Fapy•dG replication by Human DNA polymerase β.Nucleic acids research · 2024Article
- Article
- Structural Insight into Polymerase Mechanism via a Chiral Center Generated with a Single Selenium Atom.International journal of molecular sciences · 2023Article
- Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.Nature cell biology · 2023Article
- Synthesis, molecular structure and urease inhibitory activity of novelSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Light-Elicited and Oxygen-Saved Iridium Nanocapsule for Oxidative Damage Intensified Oncotherapy.Molecules (Basel, Switzerland) · 2023Article
- In crystallo observation of active site dynamics and transient metal ion binding within DNA polymerases.Structural dynamics (Melville, N.Y.) · 2023Article
- New insights into DNA polymerase mechanisms provided by time-lapse crystallography.Current opinion in structural biology · 2022Review
- 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification.Experimental & molecular medicine · 2022Review
- Visualizing the three-metal-ion-dependent cleavage of a mutagenic nucleotide.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidative stress promotes genomic instability and human diseases. A common oxidized nucleoside is 8-oxo-7,8-dihydro-2'-deoxyguanosine, which is found both in DNA (8-oxo-G) and as a free nucleotide (8-oxo-dGTP). Nucleotide pools are especially vulnerable to oxidative damage. Therefore cells encode an enzyme (MutT/MTH1) that removes free oxidized nucleotides. This cleansing function is required for cancer cell survival and to modulate Escherichia coli antibiotic sensitivity in a DNA polymerase (pol)-dependent manner. How polymerases discriminate between damaged and non-damaged nucleotides is not well understood. This analysis is essential given the role of oxidized nucleotides in mutagenesis, cancer therapeutics, and bacterial antibiotics. Even with cellular sanitizing activities, nucleotide pools contain enough 8-oxo-dGTP to promote mutagenesis. This arises from the dual coding potential where 8-oxo-dGTP(anti) base pairs with cytosine and 8-oxo-dGTP(syn) uses its Hoogsteen edge to base pair with adenine. Here we use time-lapse crystallography to follow 8-oxo-dGTP insertion opposite adenine or cytosine with human pol β, to reveal that insertion is accommodated in either the syn- or anti-conformation, respectively. For 8-oxo-dGTP(anti) insertion, a novel divalent metal relieves repulsive interactions between the adducted guanine base and the triphosphate of the oxidized nucleotide. With either templating base, hydrogen-bonding interactions between the bases are lost as the enzyme reopens after catalysis, leading to a cytotoxic nicked DNA repair intermediate. Combining structural snapshots with kinetic and computational analysis reveals how 8-oxo-dGTP uses charge modulation during insertion that can lead to a blocked DNA repair intermediate.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.