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The chemical biology of DNA damage / edited by Nicholas E. Geacintov, Suse Broyde. — Weinheim : Wiley-VCH, 2010. – (58.174252/C517) |
Contents
Contents
Preface XV
List of Contributors XVII
Part One Chemistry and Biology of DNA Lesions 1
1 Introduction and Perspectives on the Chemistry and Biology of DNA Damage 3
1.1 Overview of the Field ， 3
1.2 DNA Damage-A Constant Threat 4
1.3 DNA Damage and Disease 5
1.4 DNA Damage and Chemotherapeutic Applications 8
1.5 The Cellular DNA Damage Response (DDR) 9
1.6 Repair Mechanisms that Remove DNA Lesions 10
1.7 Relationships between the Chemical， Structural， and Biological Features of DNA Lesions 12
Acknowledgements 15
References 15
2 Chemistry of Inflammation and DNA Damage: Biological Impact of Reactive Nitrogen Species 21
2.1 Introduction 21
2.2 DNA Oxidation and Nitration 23
2.3 DNA Deamination 26
2.4 2'-Deoxyribose Oxidation 30
2.5 Indirect Base Damage Caused by RNS 35
2.6 Conclusions 38
Acknowledgements 38
References 38
3 Oxidatively Generated Damage to Isolated and Cellular DNA 53
3.1 Introduction 53
3.2 Single Base Damage 55
3.3 Tandem Base Lesions 66
3.4 Hydroxyl Radical-Mediated 2-Deoxyribose Oxidation Reactions 67
3.5 Secondary Oxidation Reactions of Bases 70
3.6 Conclusions and Perspectives 71
Acknowledgements 71
References 72
4 Role of Free Radical Reactions in the Formation of DNA Damage 81
4.1 Introduction 81
4.2 Importance of Free Radical Reactions with DNA 82
4.3 Mechanisms of Product Formation 91
4.4 Biological Implications 99
Acknowledgements 100
References 101
5 DNA Damage Caused by Endogenously Generated Products of Oxidative Stress 105
5.1 Lipid Peroxidation 105
5.2 2'-Deoxyribose Peroxidation 107
5.3 Reactions of MDA and [3-Substituted Acroleins with DNA Bases 109
5.4 Stability of MldG: Hydrolytic Ring-Opening and Reaction with Nucleophiles 112
5.5 Propano Adducts 114
5.6 Etheno Adducts 114
5.7 Mutagenicity of Peroxidation-Derived Adducts 117
5.8 Repair of DNA Damage 121
5.9 Assessment of DNA Damage 123
5.10 Conclusions 126
Acknowledgements 126
References 126
6 Polycyclic Aromatic Hydrocarbons: Multiple Metabolic Pathways and the DNA Lesions Formed 131
6.1 Introduction 131
6.2 Radical Cation Pathway 134
6.3 Diol Epoxides 137
6.4 PAH o-Quinones 141
6.5 Future Directions 147
Acknowledgements 148
References 148
7 Aromatic Amines and Heterocyclic Aromatic Amines: From Tobacco Smoke to Food Mutagens 157
7.1 Introduction 157
7.2 Exposure and Cancer Epidemiology 157
7.3 Enzymes of Metabolic Activation and Genetic Polymorphisms 159
7.4 Reactivity of N-Hydroxy-AAs and N-Hydroxy-HAAs with DNA 161
7.5 Syntheses of AA-DNA and HAA-DNA Adducts 162
7.6 Biological Effects of AA-DNA and HAA-DNA Adducts 162
7.7 Bacterial Mutagenesis 164
7.8 Mammalian Mutagenesis 165
7.9 Mutagenesis in Transgenic Rodents 166
7.10 Genetic Alterations in Oncogenes and Tumor Suppressor Genes 167
7.11 AA-DNA and HAA-DNA Adduct Formation in Experimental Animals and Methods of Detection 168
7.12 AA-DNA and HAA-DNA Adduct Formation in Humans 171
7.13 Future Directions 173
Acknowledgements 173
References 173
8 Genotoxic Estrogen Pathway: Endogenous and Equine Estrogen Hormone Replacement Therapy 185
8.1 Risks of Estrogen Exposure 185
8.2 Mechanisms of Estrogen Carcinogenesis
8.3 Estrogen Receptor as a Trojan Horse (Combined Hormonal/Chemical Mechanism) 193
8.4 Conclusions and Future Directions 194
Acknowledgements 194
References 194
Part Two New Frontiers and Challenges: Understanding Structure-Function Relationships and Biological Activity 201
9 Interstrand DNA Cross-Linking 1，N2-Deoxyguanosine Adducts Derived from α，β-Unsaturated Aldehydes: Structure-Function Relationships 203
9.1 Introduction 203
9.2 Interstrand Cross-Linking Chemistry of the y-OH-PdG Adduct (9) 205
9.3 Interstrand Cross-Linking by the c~-CH3-7-OH-PdG Adducts Derived from Crotonaldehyde 207
9.4 Interstrand Cross-Linking by 4-HNE 207
9.5 Carbinolamine Cross-Links Maintain Watson-Crick Base-Pairing 209
9.6 Role of DNA Sequence 210
9.7 Role of Stereochemistry in Modulating Cross-Linking 210
9.8 Biological Significance 212
9.9 Conclusions 213
Acknowledgements 213
References 213
10 Structure-Function Characteristics of Aromatic Amine-DNA Adducts 217
10.1 Introduction 217
10.2 Major Conformational Motifs 219
10.3 Conformational Heterogeneity 221
10.4 Structures of DNA Lesion-DNA Polymerase Complexes 231
10.5 Conclusions 232
Acknowledgements 233
References 233
11 Mechanisms of Base Excision Repair and Nucleotide Excision Repair 239
11.1 General Features of Base Excision and Nucleotide Excision Repair 239
11.2 BER 241
11.3 NER 248
11.4 Conclusions 254
References 254
12 Recognition and Removal of Bulky DNA Lesions by the Nucleotide Excision Repair System 261
12.1 Introduction 261
12.2 Overview of Mammalian NER 261
12.3 Prokaryotic NER 263
12.4 Recognition of Bulky Lesions by Mammalian NER Factors 263
12.5 Bipartite Model of Mammalian NER and the Multipartite Model of Lesion Recognition 264
12.6 DNA Lesions Derived from the Reactions of PAH Diol Epoxides with DNA are Excellent Substrates for Probing the Mechanisms of NER 265
12.7 Multidisciplinary Approach Towards Investigating Structure-Function Relationships in the NER of Bulky PAH-DNA Adducts 268
12.8 Dependence of DNA Adduct Conformations and NER on PAH Topology and Stereochemistry 269
12.9 Dependence of NER of the 10S (+)-trans-anti-B[a]P-N2-dG Adduct on Base Sequence Context 280
12.10 Conclusions 287
Acknowledgements 289
References 289
13 Impact of Chemical Adducts on Translesion Synthesis in Replicative and Bypass DNA Polymerases: From Structure to Function 299
13.1 Introduction 299
13.2 Bypass of Abasic Sites 302
13.3 Lesions Generated by Oxidative Damage to DNA 305
13.4 Exocyclic DNA Adduct Bypass 308
13.5 Alkylated DNA 310
13.6 Polycyclic Aromatic Hydrocarbons and the Effect of Adduct Size upon Polymerase Catalysis 313
13.7 Cyclobutane Pyrimidine Dimers and UV Photoproducts 316
13.8 Inter- and Intrastrand DNA Cross-Links 316
13.9 Conclusions 318
References 319
14 Elucidating Structure-Function Relationships in Bulky DNA Lesions: From Solution Structures to Polymerases 331
14.1 Introduction 331
14.2 Benzo[a]pyrene-Derived DNA Lesions as a Useful Model 331
14.3 Computational Elucidation of the Structural Properties of B[a]P-Derived DNA Lesions in Solution 333
14.4 DNA Polymerase Structure-Function Relationships Elucidated with B[a]P-Derived Lesions 335
14.5 Mechanism of the Nucleotidyl Transfer Reaction 343
14.6 Conclusions and Future Perspectives 345
Acknowledgements 345
References 346
15 Translesion Synthesis and Mutagenic Pathways in Escherichia coli Cells 353
15.1 Introduction 353
15.2 Mutagenesis in E. coli has Illuminated Our Understanding of Mutagenesis in General 354
15.3 Why Does E. coli have Three Translesion Synthesis DNA Polymerases? 356
15.4 Overview of the Steps Leading to Translesion Synthesis 358
15.5 Case Studies: AAF-C8-dG and N2-dG Adducts， Such as +BP 360
15.6 Structure-Function Analysis of Y-Family Pols IV and V of E. coli 362
15.7 Y-Family DNA Polymerase Mechanistic Steps 373
15.8 Structure of B-Family Pol II of E. coli 373
References 374
16 Insight into the Molecular Mechanism of Translesion DNA Synthesis in Human Cells using Probes with Chemically Defined DNA Lesions 381
16.1 Introduction 381
16.2 Overview of TLS 382
16.3 Plasmid Model Systems with Defined Lesions for Studying TLS 384
16.4 Gap-Lesion Plasmid Assay for Mammalian TLS 384
16.5 Some Lesions are Bypassed Most Effectively and Most Accurately by Specific Cognate TLS DNA Polymerases 387
16.6 Pivotal Role for Pol ζ in TLS Across a Wide Variety of DNA Lesions 388
16.7 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 388
16.8 Evidence that TLS Occurs by Two-Polymerase Mechanisms， in Combinations that Determine the Accuracy of the Process 391
16.9 Conclusions 393
Acknowledgements 393
References 394
17 DNA Damage and Transcription Elongation: Consequences and RNA Integrity 399
17.1 Introduction 399
17.2 DNA Repair 400
17.3 Transcription Elongation and DNA Damage 402
17.4 RNA Polymerases: A Brief Overview 402
17.5 RNA Polymerase Elongation Past DNA Damage 407
17.6 Conclusions 421
Acknowledgements 428
References 429
Index 439
