Oxidative DNA Damage and Repair Mechanisms in Biological Systems
Summary
Oxidative DNA damage arises when reactive oxygen species generated by mitochondrial respiration, inflammatory processes or environmental stressors attack nucleobases and the sugar–phosphate backbone. Among the various lesions, 8-oxoguanine is both abundant and mutagenic, as it can mispair with adenine during replication, leading to G:C→T:A transversions. To maintain genomic integrity, cells deploy the base excision repair pathway, in which specialised DNA glycosylases recognise and excise damaged bases, followed by endonuclease cleavage, gap filling by polymerases and ligation. Key proteins such as 8-oxoguanine DNA glycosylase-1 (OGG1), apurinic/apyrimidinic endonuclease 1 and poly(ADP-ribose) polymerase-1 coordinate lesion recognition and strand restoration. Beyond simple repair, oxidised bases can influence chromatin structure and transcriptional programmes, acting as epigenetic signals in redox-regulated gene expression. Recent technological advances now permit single-molecule mapping of oxidative lesions, revealing regional differences in damage accumulation and repair that shape mutation landscapes and inform therapeutic strategies.
Research from Nature Portfolio
Recent methodological developments have enabled high-resolution detection of oxidative lesions by integrating base excision repair with an expanded genetic alphabet. Following enzymatic processing of apurinic sites and 8-oxoguanine, unnatural nucleotides are installed to mark lesion positions. These modified strands can be PCR amplified and analysed by nanopore sequencing, allowing precise localisation and quantification of multiple lesions per DNA molecule. This approach offers a platform for genome-wide mapping of oxidative damage and for assessing repair efficiency under physiological and pathological conditions.
Oxidative DNA Damage and Repair Mechanisms in Biological Systems publication trend
The graph below shows the total number of articles in oxidative dna damage and repair mechanisms in biological systems across all publications each year (not limited to Nature Index journals).
Technical terms
Reactive oxygen species (ROS): Chemically reactive derivatives of oxygen that can oxidise DNA, proteins and lipids.
8-oxoguanine (8-oxoG): Oxidised form of guanine prone to mispairing with adenine, leading to point mutations.
Base excision repair (BER): DNA repair pathway that removes small base lesions via lesion recognition, excision, end processing and strand resynthesis.
DNA glycosylase: Enzyme that recognises and excises specific oxidised or otherwise modified bases to initiate BER.
References
- 8-Oxoguanine targeted by 8-oxoguanine DNA glycosylase 1 (OGG1) is central to fibrogenic gene activation upon lung injury. Nucleic Acids Research (2023).
- 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification. Experimental & Molecular Medicine (2022).
- Genomic landscape of oxidative DNA damage and repair reveals regioselective protection from mutagenesis. Genome Biology (2018).
- Identification of DNA lesions using a third base pair for amplification and nanopore sequencing. Nature Communications (2015).
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