Oxidative DNA Damage: Induction, Repair and Significance

Published

September 1, 2004

Author(s)

M D. Evans, Miral M. Dizdar, M S. Cooke

Abstract

The generation of reactive oxygen species may be both beneficial to cells, performing a function in inter- and intra-cellular signaling, and detrimental, modifying cellular bimolecules, accumulation of which has been associated with numerous diseases. Of the molecules subject to oxidative modification, DNA has received the greatest attention, with biomarkers of exposure and effect closest to validation. Despite nearly a quarter of a century of study, and a large number of base- and sugar-derived DNA lesions having been identified, the majority of studies have focused upon the guanine modification, 7,8-dihydro-8-oxo2'-deoxyguanosine (8-OH-dG). For the most part, the biological significance of other lesions has not, as yet, been investigated. In contrast, the description and characterization of enzyme systems responsible for repairing oxidative DNA base damage is growing rapidly, being the subject of intense study, However, there remain notable gaps in our knowledge of which repair proteins remove which lesions, plus, as more lesions identified, new processes/substrates need to be determined. There are many reports describing elevated levels of oxidatively modified DNA lesions, in various biological matrices, in a plethora of diseases, however, for the majority of these the association could merely be coincidental, and more detailed studies are required. Nevertheless, even based simply upon reports of studies investigating the potential role of 8-OH-dG in disease, the weight of evidence strongly suggests some link between such damage and the pathogenesis of disease. However, exact roles remain to be elucidated.

Citation

Mutation Research - Mutation Research Genomics

Volume

567

Issue

1

Pub Type

Journals

Keywords

cardiovascular disease, DNA repair, ischaemia-reperfusion injury, neurodegenerative disease, oxidative DNA damage

Citation

Evans, M. , Dizdar, M. and Cooke, M. (2004), Oxidative DNA Damage: Induction, Repair and Significance, Mutation Research - Mutation Research Genomics (Accessed May 18, 2024)