DNA Structure-Dependent Enrichment of Oxidative Lesions

Oxidative DNA lesions such as 8-oxo-7,8-dihydroguanine (8-oxoG) and abasic (AP) sites contribute to mutagenesis and genetic instability. H-DNA, a naturally occurring intramolecular triplex structure, promotes genetic instability and is susceptible to oxidative damage. Here, we examined how oxidative lesions distribute within an H-DNA-forming sequence. Although oxidative stress increased oxidized purines overall, no template-dependent differences were detected at a distal B-DNA locus. In contrast, AP sites and FPG-sensitive lesions were enriched within the H-DNA region relative to the B-DNA control, even under basal conditions. These findings indicate that H-DNA topology enhances local susceptibility to oxidative damage and shapes the spatial distribution of oxidative DNA lesions that can contribute to mutagenesis.

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Publication Details

Journal
Chemical Research in Toxicology
Published
2026-06-28
DOI
https://doi.org/10.1021/acs.chemrestox.6c00139
Primary Topic
DNA Repair Mechanisms
Type
article
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article

DNA Structure-Dependent Enrichment of Oxidative Lesions

Karen M. Vásquez, Maha Zewail‐Foote, Alex W. Klattenhoff
Chemical Research in Toxicology
DNA Repair Mechanisms
article

DNA Structure-Dependent Enrichment of Oxidative Lesions

Karen M. Vásquez, Maha Zewail‐Foote, Alex W. Klattenhoff
article en

Abstract

Oxidative DNA lesions such as 8-oxo-7,8-dihydroguanine (8-oxoG) and abasic (AP) sites contribute to mutagenesis and genetic instability. H-DNA, a naturally occurring intramolecular triplex structure, promotes genetic instability and is susceptible to oxidative damage. Here, we examined how oxidative lesions distribute within an H-DNA-forming sequence. Although oxidative stress increased oxidized purines overall, no template-dependent differences were detected at a distal B-DNA locus. In contrast, AP sites and FPG-sensitive lesions were enriched within the H-DNA region relative to the B-DNA control, even under basal conditions. These findings indicate that H-DNA topology enhances local susceptibility to oxidative damage and shapes the spatial distribution of oxidative DNA lesions that can contribute to mutagenesis.

Chemical Research in Toxicology
Southwestern University (US), The University of Texas at Austin (US)
Openalex Percentile: Top 11%
DNA Repair Mechanisms
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