ArticleNucleic acids research2018
Oxidative damage to epigenetically methylated sites affects DNA stability, dynamics and enzymatic demethylation.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Kinetics and dynamics of oligonucleotide hybridization.Nature reviews. Chemistry · 2025Review
- Global identification and functional characterization of Z-DNA in rice.Plant biotechnology journal · 2025Article
- Base Excision DNA Repair in Plants:International journal of molecular sciences · 2023Review
- DNA damage twists base choreography.Nature chemical biology · 2023Article
- The Road to Malignant Cell Transformation after Particulate Matter Exposure: From Oxidative Stress to Genotoxicity.International journal of molecular sciences · 2023Review
- From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration.Frontiers in pharmacology · 2023Review
- Article
- Oxidative Damage Induces a Vacancy G-Quadruplex That Binds Guanine Metabolites: Solution Structure of a cGMP Fill-in Vacancy G-Quadruplex in the OxidizedJournal of the American Chemical Society · 2022Article
- Clays as Vehicles for Drug Photostability.Pharmaceutics · 2022Review
- The impact of epigenetic information on genome evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Review
- Molecular Structure, Binding Affinity, and Biological Activity in the Epigenome.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
DNA damage can affect various regulatory elements of the genome, with the consequences for DNA structure, dynamics, and interaction with proteins remaining largely unexplored. We used solution NMR spectroscopy, restrained and free molecular dynamics to obtain the structures and investigate dominant motions for a set of DNA duplexes containing CpG sites permuted with combinations of 5-methylcytosine (mC), the primary epigenetic base, and 8-oxoguanine (oxoG), an abundant DNA lesion. Guanine oxidation significantly changed the motion in both hemimethylated and fully methylated DNA, increased base pair breathing, induced BI→BII transition in the backbone 3' to the oxoG and reduced the variability of shift and tilt helical parameters. UV melting experiments corroborated the NMR and molecular dynamics results, showing significant destabilization of all methylated contexts by oxoG. Notably, some dynamic and thermodynamic effects were not additive in the fully methylated oxidized CpG, indicating that the introduced modifications interact with each other. Finally, we show that the presence of oxoG biases the recognition of methylated CpG dinucleotides by ROS1, a plant enzyme involved in epigenetic DNA demethylation, in favor of the oxidized DNA strand. Thus, the conformational and dynamic effects of spurious DNA oxidation in the regulatory CpG dinucleotide can have far-reaching biological consequences.
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Registered trials
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