The chemical biology of DNA damage. (2011)

• Record Type: Book
• Further Information: Note: Edited by Nicholas E. Geacintov, Suse Broyde.
• Other Names: Geacintov, Nicholas E; Broyde, Suse
• 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;
• Publisher Details: Place of publication not identified : Wiley-VCH
• Publication Date: 2011
• Extent: 1 online resource (471 pages)
• Subjects: 572.86; DNA damage
• Languages: English
• ISBNs: 9783527642113
• Access Rights: Legal Deposit; Only available on premises controlled by the deposit library and to one user at any one time; The Legal Deposit Libraries (Non-Print Works) Regulations (UK).
• Access Usage: Restricted: Printing from this resource is governed by The Legal Deposit Libraries (Non-Print Works) Regulations (UK) and UK copyright law currently in force.