Oxidative Damage Mechanisms in Nucleic Acids
Summary
Oxidative damage to nucleic acids arises from endogenous metabolism, environmental stressors and ionising radiation, generating reactive oxygen species (ROS) that attack DNA and RNA. Key mechanisms include hydrogen‐atom abstraction from the sugar backbone, one‐electron oxidation of nucleobases and addition of oxygen radicals to aromatic rings. Common lesions encompass 8-oxo-7,8-dihydroguanine, thymine glycol and abasic sites, as well as strand breaks and cross-links. These modifications compromise genetic integrity by inducing miscoding, replication stalling and mutagenesis, and are implicated in ageing, cancer and neurodegenerative disorders. Cells deploy base excision repair, nucleotide excision repair and specialised glycosylases to excise and restore damaged sites. Recent methodological advances—in mass spectrometry, electrochemical generation of defined lesions and spectroscopic mapping—have deepened our mechanistic understanding, informing diagnostics, antioxidant therapies and precision editing of damage repair pathways.
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Oxidative Damage Mechanisms in Nucleic Acids publication trend
The graph below shows the total number of articles in oxidative damage mechanisms in nucleic acids across all publications each year (not limited to Nature Index journals).
Technical terms
Reactive oxygen species (ROS): Highly reactive derivatives of oxygen, such as superoxide and hydroxyl radicals, that attack nucleic acids and other biomolecules.
8-oxo-7,8-dihydroguanine (8-oxoG): A prevalent oxidative lesion of guanine that mispairs with adenine, leading to G→T transversions.
Hydroxyl radical (·OH): A potent oxidant formed by homolytic cleavage of water or hydrogen peroxide, capable of abstracting hydrogen atoms from sugars and bases.
Etheno adducts: Alkylation lesions in which lipid peroxidation products add to nucleobases, creating bulky, ring-opened structures.
Infrared multiple photon dissociation (IRMPD) spectroscopy: A gas-phase technique employing multiple infrared photons to fragment and structurally characterise ionic biomolecules.
References
- Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping*. Journal of Biological Chemistry (2004).
- Controlled potential electro-oxidation of genomic DNA. PLOS ONE (2018).
- Type I and Type II photosensitization of DNA etheno adducts. Photochemical & Photobiological Sciences (2024).
- OH Radical‐Induced Oxidation in Nucleosides and Nucleotides Unraveled by Tandem Mass Spectrometry and Infrared Multiple Photon Dissociation Spectroscopy. ChemPhysChem (2023).
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