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Recent Aspects of Oxidative DNA Damage: Guanine Lesions, Measurement and Substrate Specificity of DNA Repair Glycosylases

  • Jean Cadet , Sophie Bellon , Maurice Berger , Anne-Gaëlle Bourdat , Thierry Douki , Victor Duarte , Sandrine Frelon , Didier Gasparutto , Evelyne Muller , Jean-Luc Ravanat and Sylvie Sauvaigo
Published/Copyright: June 1, 2005
Biological Chemistry
From the journal Volume 383 Issue 6

Abstract

This review discusses recent aspects of oxidation reactions of DNA and model compounds involving mostly .OH radicals, oneelectron transfer process and singlet oxygen ([1]O[2]). 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-2deoxyguanosine (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 workup 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 Nglycosylases 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.

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Published Online: 2005-06-01
Published in Print: 2002-06-26

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

  1. Highlight: Environmental Mutagenesis
  2. DNA Double-Strand Break Repair by Homologous Recombination
  3. An Overview of the Analysis of DNA Methylation in Mammalian Genomes
  4. Methylation of the RASSF1A Gene in Human Cancers
  5. Exocyclic DNA Adducts as Oxidative Stress Markers in Colon Carcinogenesis: Potential Role of Lipid Peroxidation, Dietary Fat and Antioxidants
  6. DNA Polymorphisms as Modulators of Genotoxicity and Cancer
  7. Recent Aspects of Oxidative DNA Damage: Guanine Lesions, Measurement and Substrate Specificity of DNA Repair Glycosylases
  8. The Bacterial Regulatory Protein H-NS A Versatile Modulator of Nucleic Acid Structures
  9. Molecular Mechanisms of Nickel Carcinogenesis
  10. DNA Binding Properties of the Yeast Msh2-Msh6 and Mlh1-Pms1 Heterodimers
  11. N-Hydroxyarylamine O-Acetyltransferase-Deficient Escherichia coli Strains Are Resistant to the Mutagenicity of Nitro Compounds
  12. Functional Genomics of C190T Single Nucleotide Polymorphism in Human N-Acetyltransferase 2
  13. Increase in Ceramide Level Alters the Lysosomal Targeting of Cathepsin D prior to Onset of Apoptosis in HT-29 Colon Cancer Cells
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