Recent aspects of oxidative DNA damage: guanine lesions, measurement and substrate specificity of DNA repair glycosylases.
This review discusses recent aspects of oxidation reactions of DNA and model compounds involving mostly OH radicals, one-electron transfer process and singlet oxygen (1O2). Emphasis is placed on the formation of double DNA lesions involving a purine base on one hand and either a pyrimidine base or a 2-deoxyribose moiety on the other hand. Structural and mechanistic information is also provided on secondary oxidation reactions of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), a major DNA marker of oxidative stress. Another major topic which is addressed here deals with recent developments in the measurement of oxidative base damage to cellular DNA. This has been mostly achieved using the accurate and highly specific HPLC method coupled with the tandem mass spectrometry detection technique. Interestingly, optimized conditions of DNA extraction and subsequent work-up allow the accurate measurement of 11 modified nucleosides and bases within cellular DNA upon exposure to oxidizing agents, including UVA and ionizing radiations. In addition, the modified comet assay, which involves the use of bacterial DNA N-glycosylases to reveal two main classes of oxidative base damage, is applicable to isolated cells and is particularly suitable when only small amounts of biological material are available. Finally, recently available data on the substrate specificity of DNA repair enzymes belonging to the base excision pathways are briefly reviewed.
Cadet
Jean
J
Service de Chimie Inorganique et Biologique & UMR 5046, Département de Recherche Fondamentale sur la Matière Condensée, CEA/Grenoble, France.
Bellon
Sophie
S
Berger
Maurice
M
Bourdat
Anne-Gaëlle
AG
Douki
Thierry
T
Duarte
Victor
V
Frelon
Sandrine
S
Gasparutto
Didier
D
Muller
Evelyne
E
Ravanat
Jean-Luc
JL
Sauvaigo
Sylvie
S
D018736:DNA Adducts; D004249:DNA Damage / Q000235:genetics*; D011088:DNA Ligases / Q000737:chemistry* / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006147:Guanine / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D011687:Purines / Q000737:chemistry; D013379:Substrate Specificity
D018736:DNA Adducts; D011687:Purines; D006147:Guanine; D011088:DNA Ligases