Oxidative Damage to Nucleic Acids (eBook)

Drs. Mark D. Evans and Marcus S. Cooke are academics at the University of Leicester, U.K. Collectively we have around 30-35 years of research experience in the field of free radical biochemistry, most of it in relation to damage to the genome. Mark did his Bachelor’s degree at Brunel University, Uxbridge, U.K., his PhD at Louisiana State University, Baton Rouge, USA and has worked his way through the ranks at The University of Leicester via several postdocs to become a tenured non-clinical lecturer in the Department of Cancer Studies and Molecular Medicine (CSMM). Marcus did his Bachelor’s degree at John Moore’s University, Liverpool and both his MSc and PhD at University of Leicester. Marcus also worked his way through the ranks to become a tenured non-clinical senior lecturer in CSMM, but also holds a joint appointment in the world renowned Department of Genetics at Leicester, home of DNA fingerprinting. 2003 saw Marcus receive the Young Scientist Prize from the European Environmental Mutagen Society for his work on DNA damage. Our pedigree demonstrates that we are in a prime position to evaluate the cutting edge of research in the field of DNA oxidation and, in acknowledgement of this, the world’s leaders in their respective fields agreed to contribute to the book.

About the Editors... 4
CONTENTS 6
EDITORS 10
PREFACE 15
Acknowledgements 17
Oxidatively Generated Damageto Cellular DNA: Mechanistic Aspects 18
Chlorination and Nitration of DNA and Nucleic Acid Components 31
Prevention of the Mutagenicity and Cytotoxicity of Oxidized Purine Nucleotides 57
Nucleotide Incision Repair: An Alternative and Ubiquitous Pathway to Handle Oxidative DNA Damage 71
OGGl: From Structural Analysis to the Knockout Mouse 84
Processing of 3'-End Modified DNA Strand Breaks Induced by Oxidative Damage 98
Oxidative Damage and Promoter Function 108
Oxidative DNA Damage and Telomere Shortening 117
Oxidative Damage and Repair in the Mitochondrial Genome 126
The Role of Oxidative Damage to Nucleic Acids in the Pathogenesis of Neurological Disease 140
Nucleic Acid Oxidation and the Pathogenesis of Cardiovascular Diseases 158
Oxidative DNA Damage and Carcinogenesis 170
The Physiological and Pathological Roles of Oxidative Damage to DNA in Relation to Life Stage 184
Analysis of 8-Hydroxy-2'-Deoxyguanosine as a Marker of Oxidatively Damaged DNA in Relation to Carcinogenesis and Aging 195
Oxidatively Damaged DNA and Inflammation 205
The Role of Antioxidants in the Prevention of Oxidative Damage to Nucleic Acids 224
Index 241