Advances in DNA Damage and Repair

Damage to DNA by both exogenous and endogenous sources is increasingly regarded as highly important in the initiation and progression of cancer and in the occurance of other pathological events. DNA damage caused by reactive oxygen-derived species, also called oxidative DNA damage, is most the frequent type encountered by aerobic cells. Mechanistic studies of carcinogenesis indicate an important role of this type of damage to DNA. There is also strong evidence to support the role of oxidative DNA damage in the aging process. DNA damage is opposed in vivo by repair systems. If not repaired, DNA damage may lead to detrimental biological consequences. Therefore, the repair of DNA damage is regarded as one of the essential events in all life forms. In recent years the field of DNA repair has flourished due to new findings on DNA repair mechanisms and the molecular basis of cancer. A detailed knowledge of mechanisms of DNA damage and repair, and how individual repair enzymes function may lead to manipulation of DNA repair in cells and ultimately to an increase of the resistence of human cells to DNA-damaging agents. This volume covers the most recent devlopments in this research field and contains contributions from scientists working in the fields of biochemistry, molecular biology, enzymology, biomedical science, and radiation biology.

Zusammenfassung
Proceedings of a NATO ASI held in Tekirova Antalya, Turkey, October 14-24, 1997

Inhalt

1. Mapping Reactive Oxygen-Induced DNA Damage at Nucleotide Resolution.- 2. Application of Oxidative DNA Damage Measurements to Study Antioxidant Actions of Dietary Components.- 3. DNA Repair and Transcription in Premature Aging Syndromes.- 4. Excision Repair of 8-Oxoguanine in Eukaryotes: The Oggl Proteins.- 5. Oxidative Base Damage to DNA: Recent Mechanistic Aspects, Measurement and Repair.- 6. Roles of AP Endonucleases in Repair and Genetic Stability.- 7. Mechanisms of Oxidative DNA Damage; Lesions and Their Measurement.- 8. Drosophila Ribosomal Protein S3 Contains N-Glycosylase, Abasic Site, and Deoxyribophosphodiesterase DNA Repair Activities.- 9. Bypass of DNA Damage by RNA Polymerases: Implications for DNA Repair and Transcriptional Mutagenesis.- 10. The Current Status of Nucleotide Excision Repair in the Yeast Saccharomyces cerevisiae.- 11. Physiological Chemistry of Superoxide and Nitric Oxide Interactions: Implications in DNA Damage and Repair.- 12. Recognition and Excision of Bases from Oxidatively Damaged DNA by Fpg, Oggl, and MutY Proteins.- 13. DNA Repair as a Susceptibility Factor in Chronic Diseases in Human Populations.- 14. Transcription-Coupled DNA Repair: Which Lesions? Which Diseases?.- 15. Genotoxicity Tests: Application to Occupational Exposure as Biomarkers.- 16. Studies on Oxidative Mechanisms of Metal-Induced Carcinogenesis: Recent Developments.- 17. Mechanism of Action of Escherichia coli Formamidopyrimidine N-Glycosylase and Endonuclease V.- 18. Human Uracil-DNA Glycosylase: Gene Structure, Regulation, and Structural Basis for Catalysis.- 19. Repair of DNA Damaged by Free Radicals.- 20. DNA Lesions Generated in Vivo by Reactive Oxygen Species, Their Accumulation and Repair.- 21. DNA Damage by Iron and Hydrogen Peroxide.- 22. Measurement of Oxidative Damage to DNA Nucleobases in Vivo: Interpretation of Nuclear Levels and Urinary Excretion of Repair Products.- 23. Effects of Vitamin E Supplementation on in Vivo Oxidative DNA Damage.- 24. Repair of Oxidative DNA Damage and Aging: Central Role of AP-Endonuclease.- 25. Action of Antioxidants against Oxidative Stress.- 26. 8-Hydroxyguanine, DNA Adduct Formed by Oxygen Radicals: From Its Discovery to Current Studies on Its Involvement in Mutagenesis and Repair.- 27. DNA Damage Induced by Reactive Nitrogen Species.- 28. Modification of Ionizing Radiation Damage to Cellular DNA by Factors Affecting Chromatin Structure: Effects of Histone Deacetylase Inhibitors Trichostatin A and Sodium Butyrate.- 29. Estimation of Free Radical Induced DNA Base Damages in Cancerous- and HIV Infected Patients and in Healthy Subjects.- 30. p53 Tumor Suppressor Gene: Its Role in DNA Damage Response and Cancer.- 31. Molecular Mechanism of Nucleotide Excision Repair in Mammalian Cells.- 32. Detection of 8-Hydroxy-2'-Deoxyguanosine by a Monoclonal Antibody N45.1 and Its Application.- 33. Mechanistic Studies of Radiation-Induced DNA Damage.- 34. Processing and Consequences of Oxidative DNA Base Lesions.- 35. Ionizing Radiation Damage to DNA: A Challenge to Repair Systems.- Abstracts.- Participants.- Participants Photo.- Author Index.