ArticleProceedings of the National Academy of Sciences of the United States of America2012
Defects in purine nucleotide metabolism lead to substantial incorporation of xanthine and hypoxanthine into DNA and RNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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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
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Influence of xanthine oxidase inhibitors on all-cause mortality in adults: a systematic review and meta-analysis.Cardiology journal · 2024Pooled it
- 7-Deaza-2'-Deoxyxanthosine: Impact of Halogens and Vinyl Side Chains on Purine-Purine Base Pairs in Watson-Crick DNA, Functionalization by Bioorthogonal Inverse-Electron-Demand Diels-Alder Reaction, and Mismatch Discrimination.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- De novo or Salvage? Nucleotide Availability as a Driver of Bacterial Adaptation and Virulence.MicrobiologyOpen · 2026Review
- ENDONUCLEASE V: FROM TRANSCRIPTOME REGULATOR TO CHEMICAL BIOLOGY TOOL.ChemistryEurope · 2026Article
- Inosine misincorporation into mRNA triggers the integrated stress response and activates an innate immune gene expression signature.bioRxiv : the preprint server for biology · 2026Article
- RNA Structure and Its Function.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Changes in Serum Proteins in Firefighters Responding to the 2025 Los Angeles Urban Conflagrations.Journal of occupational and environmental medicine · 2026Article
- Human MutLα activates methylpurine DNA glycosylase to induce alkylation damage cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
- Metabolomic profiling reveals that the heterogeneity of microhabitats can assist intertidal mollusks in surviving extreme cold events.Marine life science & technology · 2025Article
- Hypoxanthine activates PI3K/AKT pathway and lipid metabolism, hallmarks in breast cancer metastasis.Medical oncology (Northwood, London, England) · 2025Article
- Vulnerable Nucleotide Pools and Genomic Instability in Yeast Strains with Deletion of theInternational journal of molecular sciences · 2025Article
- Differential effects of inosine monophosphate dehydrogenase (IMPDH/GuaB) inhibition inJournal of bacteriology · 2024Article
- Base preference for inosine 3'-riboendonuclease activity of human endonuclease V: implications for cleavage of poly-A tails containing inosine.Scientific reports · 2024Article
- Emerging Roles of Xanthine Oxidoreductase in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- An ITPA Enzyme with Improved Substrate Selectivity.The protein journal · 2024Article
- Evolution of two metabolic genes involved in nucleotide and amino acid metabolism in Pseudomonas aeruginosa.PloS one · 2024Article
- Combined metabolome and transcriptome analyses reveal that growing under Red shade affects secondary metabolite content in Huangjinya green tea.Frontiers in genetics · 2024Article
- Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke.Theranostics · 2024Article
- Incorporation of inosine into DNA by human polymerase eta (Polη): kinetics of nucleotide misincorporation and structural basis for the mutagenicity.The Biochemical journal · 2023Article
- Multi-Omics Analysis of NCI-60 Cell Line Data Reveals Novel Metabolic Processes Linked with Resistance to Alkylating Anti-Cancer Agents.International journal of molecular sciences · 2023Article
5 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
9 authors at 4 institutions in 1 country.
Funding
Abstract
Deamination of nucleobases in DNA and RNA results in the formation of xanthine (X), hypoxanthine (I), oxanine, and uracil, all of which are miscoding and mutagenic in DNA and can interfere with RNA editing and function. Among many forms of nucleic acid damage, deamination arises from several unrelated mechanisms, including hydrolysis, nitrosative chemistry, and deaminase enzymes. Here we present a fourth mechanism contributing to the burden of nucleobase deamination: incorporation of hypoxanthine and xanthine into DNA and RNA caused by defects in purine nucleotide metabolism. Using Escherichia coli and Saccharomyces cerevisiae with defined mutations in purine metabolism in conjunction with analytical methods for quantifying deaminated nucleobases in DNA and RNA, we observed large increases (up to 600-fold) in hypoxanthine in both DNA and RNA in cells unable to convert IMP to XMP or AMP (IMP dehydrogenase, guaB; adenylosuccinate synthetase, purA, and ADE12), and unable to remove dITP/ITP and dXTP/XTP from the nucleotide pool (dITP/XTP pyrophosphohydrolase, rdgB and HAM1). Conversely, modest changes in xanthine levels were observed in RNA (but not DNA) from E. coli lacking purA and rdgB and the enzyme converting XMP to GMP (GMP synthetase, guaA). These observations suggest that disturbances in purine metabolism caused by known genetic polymorphisms could increase the burden of mutagenic deaminated nucleobases in DNA and interfere with gene expression and RNA function, a situation possibly exacerbated by the nitrosative stress of concurrent inflammation. The results also suggest a mechanistic basis for the pathophysiology of human inborn errors of purine nucleotide metabolism.
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Registered trials
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