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Author:   Nicholas E. Geacintov (New York University, New York, USA) ,  Suse Broyde (New York University, New York, USA)
Publisher:   Wiley-VCH Verlag GmbH
Imprint:   Blackwell Verlag GmbH
Dimensions:   Width: 17.80cm , Height: 2.70cm , Length: 24.60cm
Weight:   0.993kg
ISBN:  

9783527322954

ISBN 10:   3527322957
Pages:   471
Publication Date:   23 June 2010
Audience:   Professional and scholarly ,  Professional & Vocational
Format:   Hardback
Publisher's Status:   Out of Print
Availability:   In Print  
Limited stock is available. It will be ordered for you and shipped pending supplier's limited stock.

Table of Contents

Preface PART I: Chemistry and Biology of DNA Lesions INTRODUCTION AND PERSPECTIVES ON THE CHEMISTRY AND BIOLOGY OF DNA DAMAGE Overview of the Field DNA Damage ¿ A Constant Threat DNA Damage and Disease DNA Damage and Chemotherapeutic Applications The Cellular DNA Damage Response (DDR) Repair Mechanisms that Remove DNA Lesions Relationships between the Chemical, Structural, and Biological Features of DNA Lesions CHEMISTRY OF INFLAMMATION AND DNA DAMAGE: BIOLOGICAL IMPACT OF REACTIVE NITROGEN SPECIES Introduction DNA Oxidation and Nitration DNA Deamination 2¿-Deoxyribose Oxidation Indirect Base Damage Caused by RNS Conclusions OXIDATIVELY GENERATED DAMAGE TO ISOLATED AND CELLULAR DNA Introduction Single Base Damage Tandem Base Lesions Hydroxyl Radical-Mediated 2-Deoxyribose Oxidation Reactions Secondary Oxidation Reactions of Bases Conslusions and Perspectives ROLE OF FREE RADICAL REACTIONS IN THE FORMATION OF DNA DAMAGE Introduction Importance of Free Radical Reactions with DNA Mechanisms of Product Formation Biological Implications DNA DAMAGE CAUSED BY ENDOGENOUSLY GENERATED PRODUCTS OF OXIDATIVE STRESS Lipid Peroxidation 2¿-Deoxyribose Peroxidation Reactions of MDA and Beta-Substituted Acroleins with DNA Bases Stability of M1dG: Hydrolytic Ring-Opening and Reaction with Nucleophiles Propano Adducts Etheno Adducts Mutagenicity of Peroxidation-Derived Adducts Repair of DNA Damage Assessment of DNA Damage Conclusions POLYCYCLIC AROMATIC HYDROCARBONS: MULTIPLE METABOLIC PATHWAYS AND THE DNA LESIONS FORMED Introduction Radical Cation Pathway Diol Epoxides PAH o-Quinones Future Directions AROMATIC AMINES AND HETEROCYCLIC AROMATIC AMINES: FROM TOBACCO SMOKE TO FOOD MUTAGENS Introduction Exposure and Cancer Epidemiology Enzymes of Metabolic Activation and Genetic Polymorphisms Reactivity of N-Hydroxy-AAs and N-Hydroxy-HAAs with DNA Synthesis of AA-DNA and HAA-DNA Adducts Biological Effects of AA-DNA and HAA-DNA Adducts Biological Effects of AA-DNA and HAA-DNA Adducts Bacterial Mutagenesis Mammalian Mutagenesis Mutagenesis in Transgenic Rodents Genetic Alterations in Oncogenes and Tumor Suppressor Genes AA-DNA and HAA-DNA Adduct Formation in Humans Future Directions GENOTOXIC ESTROGEN PATHWAY: ENDOGENOUS AND EQUINE ESTROGEN HORMONE REPLACEMENT THEORY Risks of Estrogen Exposure Mechanisms of Estrogen Carcinogenesis Estrogen Receptor as a Trojan Horse (Combined Hormonal/Chemical Mechanism) Conclusions and Future Directions PART II: New Frontiers and Challenges: Understanding Structure-Function Relationships and Biological Activity INTERSTRAND DNA CROSS-LINKING 1,N2-DEOXYGUANOSINE ADDUCTS DERIVED FROM ALPHA, BETA-UNSATURATED ALDEHYDES: STRUCTURE-FUNCTION RELATIONSHIPS Introduction Interstrand Cross-Linking Chemistry of the Gamma-OH-PdG Adduct (9) Interstrand Cross-Linking by the Alpha-CH3-Yamma-OH-PG Adducts Derived from Crotonaldehyde Interstrand Cross-Linking by 4-HNE Carbinolamine Cross-Links Maintain Watson-Crick Base-Pairing Role of DNA Sequence Role of Stereochemistry in Modulating Cross-Linking Biological Significance Conclusions STRUCTURE-FUNCTION CHARACTERISTICS OF AROMATIC AMINE-DNA ADDUCTS Introduction Major Conformational Motifs Conformational Heterogeneity Structures of DNA Lesion-DNA Polymerase Complexes Conclusions MECHANISMS OF BASE EXCISION REPAIR AND NUCLEOTIDE EXCISION REPAIR General Features of Base Excision and Nucleotide Excision Repair BER NER Conclusions RECOGNITION AND REMOVAL UF BULKY DNA LESIONS BY THE NUCLEOTIDE EXCISION REPAIR SYSTEM Introduction Overview of Mammalian NER Prokaryotic NER Recognition of Bulky Lesions by Mammalian NER Factors Bipartite Model of Mammalian NER and the Multipartite Model of Lesion Recognition DNA Lesions Derived from the Reactions of PAH Diol Epoxides with DNA are Excellent Substrates for Probing the Mechanisms of NER Multidisciplinary Approach Towards Investigating Structure-Function Relationships in the NER of Bulky PAH-DNA Adducts Dependence of DNA Adduct Conformations and NER on PAH Topology and Stereochemistry Dependence of NER of the 10S (+)-trans-anti-B[a]P-N2-dG Adduct on Base Sequence Context Conclusions IMPACT OF CHEMICAL ADDUCTS ON TRANSLESION SYNTHESIS IN REPLICATIVE AND BYPASS DNA POLYMERASES: FROM STRUCTURE TO FUNCTION Introduction Bypass of Abasic Sites Lesions Generated by Oxidative Damage to DNA Exocyclic DNA Adduct Bypass Alkylated DNA Polycyclic Aromatic Hydrocarbons and the Effect of Adduct Size upon Polymerase Catalysis Cyclobutane Pyrimidine Dimers and UV Photoproducts Inter- and Intrastrand DNA Cross-Links Conclusions ELUCIDATING STRUCTURE-FUNCTION RELATIONSHIPS IN BULKY DNA LESIONS: FROM SOLUTION STRUCTURES TO POLYMERASES Introduction Benzo[a]pyrene-Derived DNA Lesions as a Useful Model Computational Elucidation of the Structural Properties of B[a]P-Derived DNA Lesions in Solution DNA Polymerase Structure-Function Relationships Elucidated with B[a]P-Derived Lesions Mechanism of the Nucleotidyl Transfer Reaction Conclusions and Future Perspectives TRANSLESION SYNTHESIS AND MUTAGENIC PATHWAYS IN ESCHERICHIA COLI CELLS Introduction Mutagenesis in E. coli has Illuminated Our Understanding of Mutagenesis in General Why Does E. coli have Three Translesion Synthesis DNA Polymerases? Overview of the Steps Leading to Translesion Synthesis Case Studies: AAF-C8-dG and N2-dG Adducts, Such as +BP Structure-Function Analysis of Y-Family Pols IV and V of E. coli Y-Family DNA Polymerase Mechanistic Steps Structure of B-Family Pol II of E. coli INSIGHT INTO THE MOLECULAR MECHANISM OF TRANSLESION DNA SYNTHESIS IN HUMAN CELLS USING PROBES WITH CHEMICALLY DEFINED DNA LESIONS Introduction Overview of TLS Plasmid Model Systems with Defined Lesions for Studying TLS Gap-Lesion Plasmid Assay for Mammalian TLS Some Lesions are Bypassed Most Effectively and Most Accurately by Specific Cognate TLS DNA Polymerases Pivotal Role for Pol Zeta in TLS Across a Wide Variety of DNA Lesions Knocking-Down the Expression of TLS Polymerases using Small INterfering RNA Provides a useful Tool for the Analysis of TLS using the Gapped Plasmid Assay Evidence that TLS Occurs by Two-Polymerase Mechanisms, in Combinations that Determine the Accuracy of the Process Conclusions DNA DAMAGE AND TRANSCRIPTION ELONGATION: CONSEQUENCES AND RNA INTEGRITY Introduction DNA Repair Transcription Elongation and DNA Damage RNA Polymerases: A Brief Overview RNA Polymerase Elongation Past DNA Damage Conclusions

Reviews

"""I believe that it will serve as a good reference book for many researchers in the field and provide a basis for research."" (The British Toxicology Society, 1 May 2011)"

I believe that it will serve as a good reference book for many researchers in the field and provide a basis for research. (The British Toxicology Society, 1 May 2011)

Author Information

Nicholas E. Geacintov is Professor of Chemistry and former Chair of the Department of Chemistry at New York University (NYU), USA. He received his PhD degree in physical chemistry and polymer chemistry from the State University of New York College of Forestry at Syracuse University, and spent most of his career at NYU. His current research interests are focused on the mechanisms of chemical carcinogenesis and oxidatively generated DNA damage, especially the relationships between the structural features of DNA lesions and their impact on DNA repair and replication. He has published over 350 papers and is currently serving as a member of the Editorial Board of the Journal of Biological Chemistry. Suse Broyde is Professor of Biology and Affiliate Professor of Chemistry at New York University, USA. Her research interests are focused on computer modeling of DNA lesions, with the goal of elucidating the molecular origins of their mutagenic and tumorigenic properties. She holds a PhD degree in physical chemistry with a minor in physics from the Polytechnic Institute of New York, and has published over 160 papers in peer-reviewed journals. She has been a member of the Editorial Advisory Board of Chemical Research in Toxicology.

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