| Preface |
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iii | |
| Contributors |
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xvii | |
| Part I. Mechanisms Of Damage Recognition: Theoretical Considerations |
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1 Dynamics of DNA Damage Recognition |
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3 | (18) |
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3 | (1) |
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2 Role of DNA Flexibility in Sequence-Dependent Activity of UDG |
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4 | (4) |
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3 Opening and Bending Dynamics of G·U Mismatches in DNA |
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8 | (5) |
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13 | (2) |
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15 | (6) |
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2 In Search of Damaged Bases |
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21 | (12) |
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21 | (1) |
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2 Mechanism for an Increased Rate of Target Site Location |
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21 | (2) |
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3 In Vitro Evidence for Processive Nicking Activity of DNA Glycosylases |
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23 | (3) |
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4 Discovery and Significance of In Vivo Processive Nicking Activity by T4-pdg |
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26 | (1) |
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5 DNA Bending as a Potential Prerequisite for Nucleotide Flipping |
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27 | (2) |
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6 Mechanisms of Nucleotide Flipping |
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29 | (1) |
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7 Specificity of Glycosylase Binding Sites and Catalytic Activities |
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30 | (1) |
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31 | (2) |
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3 Increased Specificity and Efficiency of Base Excision Repair Through Complex Formation |
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33 | (32) |
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33 | (3) |
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2 DNA Lesion Recognition and Removal |
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36 | (6) |
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42 | (4) |
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4 Gap Filling and Religation |
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46 | (3) |
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49 | (3) |
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52 | (2) |
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54 | (1) |
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54 | (1) |
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55 | (10) |
| Part II. UV Damage And Other Bulky DNA-Adducts |
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65 | (232) |
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4 Structure and Properties of DNA Photoproducts |
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67 | (28) |
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67 | (2) |
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2 Cyclobutane Pyrimidine Dimers |
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69 | (10) |
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3 Other Dimer-Related Products |
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79 | (2) |
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81 | (5) |
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86 | (2) |
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88 | (1) |
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89 | (1) |
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90 | (1) |
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90 | (5) |
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5 Damage Recognition by DNA Photolyases |
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95 | (16) |
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1 Overview of Photolyases |
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95 | (1) |
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2 The Nature of the Substrates |
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96 | (1) |
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3 Characterization of Substrate Binding and Discrimination by Photolyases |
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97 | (1) |
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4 Interactions at the Photolyase-Photoproduct Interface: The Molecular Basis for Substrate Binding and Discrimination |
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98 | (7) |
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5 Substrate Binding In Vivo |
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105 | (2) |
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6 Summary and Future Directions |
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107 | (1) |
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107 | (4) |
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6 Damage Recognition by the Bacterial Nucleotide Excision Repair Machinery |
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111 | (28) |
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111 | (2) |
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2 Diversity of DNA Lesions Recognized |
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113 | (1) |
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3 The Proteins and Their Structural Domains |
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114 | (9) |
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4 Reaction Pathway for Damage Detection and Processing |
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123 | (7) |
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5 DNA Damage Recognition within the Biological Context of the Cell |
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130 | (3) |
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6 Similarities in Damage Recognition and Verification Between Bacterial and Eukaryotic Nucleotide Excision Repair Systems |
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133 | (1) |
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133 | (6) |
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7 Recognition of DNA Damage During Eukaryotic Nucleotide Excision Repair |
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139 | (26) |
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139 | (1) |
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2 Nucleotide Excision Repair Substrates |
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139 | (1) |
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3 Eukaryotic NER Reaction |
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140 | (2) |
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4 Subunits of the Eukaryotic NER Machinery |
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142 | (1) |
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5 Stepwise Assembly of the Mammalian NER Recognition Complex |
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143 | (1) |
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6 A Preassembled Repairosome in Yeast? |
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144 | (2) |
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7 Role of Damaged DNA Binding in Damage Recognition |
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146 | (1) |
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8 Recognition of Bulky Lesions During Transcription-Coupled DNA Repair |
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147 | (1) |
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9 Bipartite Substrate Discrimination in the GGR Pathway |
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148 | (1) |
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10 XPC-hHR23B as a Sensor of Defective Base Pairing |
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149 | (2) |
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11 Transcription Factor IIH as a Sensor of Defective Deoxyribonucleotide Chemistry |
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151 | (2) |
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12 Role of XPA-RPA in Integrating Different Recognition Signals |
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153 | (2) |
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13 Damage-Specific Recruitment of XPG and XPF-ERCC1 |
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155 | (1) |
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14 Regulation of the Damage Recognition Process |
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155 | (3) |
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158 | (1) |
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159 | (6) |
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8 Interactions of the Transcription Machinery with DNA Damage in Prokaryotes |
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165 | (16) |
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165 | (3) |
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2 The Behavior of RNA Polymerase Complexes with Different Types of DNA Damage |
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168 | (2) |
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3 The Behavior of RNA Polymerase Complexes at Lesions and NER |
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170 | (3) |
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4 The Behavior of RNA Polymerase Complexes at Lesions and BER |
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173 | (2) |
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5 Summary and Future Directions |
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175 | (1) |
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175 | (6) |
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9 DNA Repair in Actively Transcribed Genes in Eukaryotic Cells |
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181 | (20) |
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181 | (1) |
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2 Heterogeneity of DNA Repair |
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182 | (3) |
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3 Methods for Detecting TCR and GGR |
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185 | (3) |
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4 DNA Repair in Transcriptionally Active Genes in Different Organisms |
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188 | (5) |
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5 Models of TCR in Eukaryotic Cells |
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193 | (1) |
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6 Effect of Different Kinds of DNA Damage on TCR |
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194 | (1) |
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195 | (6) |
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10 Chromatin Structure and the Repair of UV Light-Induced DNA Damage |
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201 | (22) |
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201 | (1) |
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2 Nucleosomes: Heterogeneity in a Conserved Structure |
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202 | (1) |
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3 Dynamic Properties of Nucleosomes Regulate DNA Accessibility |
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203 | (5) |
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4 Damage Tolerance of Nucleosomes |
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208 | (1) |
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5 Repair of Nucleosomes by Photolyase |
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209 | (2) |
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6 Repair of Nucleosomes by NER |
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211 | (3) |
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7 Site-Specific Repair in Nucleosome and Damage Recognition |
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214 | (1) |
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8 Chromatin Remodeling and DNA Repair |
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214 | (2) |
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216 | (1) |
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216 | (7) |
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11 The Ultraviolet Damage Endonuclease (UVDE) Protein and Alternative Excision Repair: A Highly Diverse System for Damage Recognition and Processing |
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223 | (16) |
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223 | (1) |
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2 Discovery and Initial Characterization of S. pombe UVDE |
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224 | (2) |
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3 Recognition and Processing of UV Photoproducts |
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226 | (1) |
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4 Recognition and Processing of Platinum G-G Diadducts |
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227 | (1) |
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5 Recognition and Processing of Abasic Sites |
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227 | (2) |
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6 Modified Bases not Recognized by UVDE |
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229 | (1) |
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7 Recognition and Processing of Base-Base Mismatches |
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230 | (1) |
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8 Recognition and Processing of Insertion-Deletion Loops |
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231 | (1) |
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9 Subsequent Steps Following UVDE-Initiated Alternative Excision Repair |
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232 | (1) |
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10 Schizosaccharomyces pombe UVDE Homologs |
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233 | (1) |
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234 | (1) |
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234 | (5) |
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12 Structural Aspects of Pt-DNA Adduct Recognition by Proteins |
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239 | (24) |
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239 | (1) |
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239 | (1) |
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3 Structural Consequences of Platinum-Binding to Double-Stranded DNA |
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240 | (5) |
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4 Recognition of cis-DDP-1,2 Intrastrand Cross-Link by Cellular Proteins |
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245 | (9) |
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254 | (1) |
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255 | (8) |
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13 Structural Aspects of Polycyclic Aromatic Carcinogen-Damaged DNA and Its Recognition by NER Proteins |
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263 | (34) |
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263 | (2) |
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2 Metabolism of PAH to Diol Epoxides and Formation of Stereoisomeric DNA Adducts |
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265 | (2) |
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267 | (2) |
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4 PAH-DNA Adducts: Conformational Motifs |
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269 | (4) |
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5 Insights into the Structural Motifs at the Nucleoside Adduct Level Derived from Computational Approaches |
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273 | (1) |
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6 PAH-DNA Adduct Conformational Motifs and NER |
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274 | (2) |
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7 Structural Differences Between Bay and Fjord Stereoisomeric PAH-/V6-Adenine Adducts and Correlations with NER Susceptibilities |
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276 | (3) |
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279 | (10) |
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289 | (1) |
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290 | (7) |
| Part III. Non-Bulky Base Damage |
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297 | (164) |
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14 Structural Features of DNA Glycosylases and AP Endonucleases |
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299 | (24) |
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1 The Base Excision Repair Pathway |
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299 | (1) |
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2 DNA Glycosylase Structural Families |
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300 | (3) |
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3 Specific Mechanisms for Recognition of Damage |
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303 | (10) |
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313 | (2) |
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315 | (1) |
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315 | (8) |
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15 Repair of Oxidized Bases |
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323 | (16) |
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1 Biological Consequences of Oxidative Damage |
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323 | (3) |
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2 Major Repair Enzymes that Recognize Oxidative Base Damage |
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326 | (7) |
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3 Repair Pathways for Oxidative DNA Damage |
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333 | (2) |
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335 | (1) |
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335 | (4) |
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16 Recognition of Alkylating Agent Damage in DNA |
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339 | (50) |
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1 Modification of DNA by Small Alkylating Agents |
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339 | (2) |
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2 DNA Repair Systems for Removal of Alkylating Agent Damage |
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341 | (1) |
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3 06-Alkylguanine DNA Methyltransferases-AGTs |
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342 | (13) |
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4 AlkB-2-oxoglutarate-Dependent Fe(II)-Dependent Oxygenases |
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355 | (7) |
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5 DNA Glycosylases-Base Excision Repair |
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362 | (15) |
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6 Nucleotide Excision Repair |
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377 | (5) |
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382 | (7) |
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17 Deaminated Bases in DNA |
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389 | (14) |
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389 | (1) |
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2 Lesions and Their Consequences |
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389 | (1) |
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390 | (3) |
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4 Endonuclease V, An Enzyme Specific for Deaminated Purines |
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393 | (3) |
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5 Hypoxanthine/Alkylpurine DNA Glycosylases |
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396 | (3) |
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6 Endonuclease VIII of E. coli |
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399 | (1) |
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399 | (1) |
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399 | (4) |
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18 New Paradigms for DNA Base Excision Repair in Mammals |
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403 | (18) |
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403 | (1) |
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2 Oxidized Base-Specific Glycosylases in E. coli and Mammals |
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404 | (12) |
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416 | (1) |
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417 | (4) |
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19 Recognition and Repair of Abasic Sites |
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421 | (24) |
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1 AP Site Formation and Biological Impact |
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421 | (2) |
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2 AP-DNA Dynamics and Structure |
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423 | (2) |
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425 | (1) |
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4 AP Site Recognition and Processing |
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426 | (6) |
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5 AP Site Repair in General |
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432 | (4) |
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436 | (9) |
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20 Oxidative Mitochondrial DNA Damage Resistance and Repair |
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445 | (16) |
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445 | (1) |
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2 General Features of Human mtDNA |
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446 | (3) |
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3 Oxidative mtDNA Damage Resistance and Repair |
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449 | (3) |
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4 New Lessons About Oxidative mtDNA Damage from the Budding Yeast, S. cerevisiae, Genetic Model System |
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452 | (3) |
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5 Conclusions and New Horizons |
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455 | (1) |
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456 | (5) |
| Part IV. Mismatch Repair |
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461 | (32) |
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21 Mechanism of DNA Mismatch Repair from Bacteria to Human |
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463 | (20) |
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463 | (3) |
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2 Biochemistry of Mismatch Repair Proteins |
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466 | (3) |
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3 Mechanism of Mismatch Repair |
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469 | (5) |
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474 | (1) |
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475 | (8) |
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22 Interaction of the Escherichia coli Vsr with DNA and Mismatch Repair Proteins |
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483 | (10) |
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483 | (2) |
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485 | (5) |
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3 Summary and Concluding Remarks |
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490 | (1) |
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490 | (3) |
| Part V. Replication And Bypass Of DNA Lesions |
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493 | (86) |
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23 Mechanism of Translesion DNA Synthesis in Escherichia coli |
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495 | (12) |
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495 | (1) |
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2 Translesion DNA Synthesis and the SOS Response |
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496 | (1) |
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497 | (1) |
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497 | (1) |
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498 | (1) |
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6 Accessory Proteins Are Required for Lesion Bypass By Pol V |
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499 | (2) |
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7 Other DNA Polymerases Involved in TLS in E. coli |
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501 | (1) |
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502 | (1) |
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503 | (4) |
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24 Mechanism of Bypass Polymerases in Eukaryotes |
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507 | (22) |
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507 | (2) |
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2 Concepts of Translesion Synthesis |
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509 | (1) |
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3 Translesion Polymerases |
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510 | (3) |
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4 Mechanistic Models of Translesion Synthesis |
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513 | (2) |
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5 Translesion Synthesis of Various DNA Damage in Eukaryotes |
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515 | (5) |
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6 Importance of Translesion Synthesis in Eukaryotic Biology |
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520 | (1) |
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521 | (8) |
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25 Structural Features of Bypass Polymerases |
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529 | (20) |
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529 | (6) |
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2 DNA Synthesis by the DINB Family Members from the Sulfolobus Genus |
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535 | (6) |
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3 DNA Binding and Lesion Bypass in Polo |
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541 | (2) |
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4 Recruitment of Y-Family DNA Polymerases |
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543 | (2) |
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5 Lesion Specificity of the Y-Family DNA Polymerases |
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545 | (1) |
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546 | (3) |
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26 Regulation of Damage Tolerance by the RAD6 Pathway |
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549 | (30) |
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549 | (1) |
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2 Mechanisms of Damage Bypass |
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550 | (4) |
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554 | (12) |
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4 Proliferating Cell Nuclear Antigen Modification by the Ubiquitin-Like Protein Sumo |
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566 | (1) |
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5 Mechanistic Considerations |
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567 | (3) |
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6 Interactions of the RAD6 Pathway with Other Factors |
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570 | (3) |
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573 | (1) |
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574 | (5) |
| Part VI. DNA Strand Breaks |
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579 | (176) |
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27 Biochemical and Cellular Aspects of Homologous Recombination |
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581 | (28) |
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581 | (1) |
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2 DNA Double-Strand Break Repair Through Homologous Recombination |
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582 | (1) |
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3 Biochemical Properties of Homologous Recombination Proteins |
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582 | (4) |
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4 Cellular Properties of Homologous Recombination Proteins |
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586 | (16) |
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602 | (7) |
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28 The Mechanism of Vertebrate Nonhomologous DNA End Joining and Its Role in Immune System Gene Rearrangements |
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609 | (20) |
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609 | (1) |
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2 Essential Aspects of Vertebrate Nonhomologous DNA End Joining (NHEJ) |
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609 | (4) |
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3 Overview of V(D)J Recombination and its Utilization of NHEJ in the Rejoining Process |
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613 | (2) |
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4 Overview of Immunoglobulin Class Switch Recombination and its Utilization of NHEJ in the Rejoining Process |
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615 | (4) |
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5 Points of Biochemical Detail in the NHEJ Pathway |
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619 | (3) |
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6 Special Aspects of NHEJ as it Relates to V(D)J Recombination |
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622 | (1) |
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7 Are There Multiple NHEJ Pathways? |
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622 | (2) |
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624 | (1) |
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9 Future Avenues of Study of the NHEJ Pathway |
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624 | (1) |
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624 | (5) |
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29 Structural Aspects of Ku and the DNA-Dependent Protein Kinase Complex |
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629 | (56) |
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629 | (5) |
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634 | (14) |
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648 | (7) |
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4 DNA-PK, Telomeres and Genomic Stability |
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655 | (7) |
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662 | (1) |
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663 | (22) |
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30 Cellular Functions of Mammalian DNA Ligases |
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685 | (20) |
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685 | (1) |
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686 | (1) |
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686 | (1) |
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687 | (6) |
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5 Cellular Functions of DNA Ligase |
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693 | (4) |
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697 | (8) |
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31 The Mrell/Rad5O/Nbs1 Complex |
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705 | (18) |
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705 | (1) |
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706 | (4) |
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3 Cellular Biochemistry of the Mre11 Complex |
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710 | (4) |
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4 Structural Biochemistry of the Mrell Complex |
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714 | (3) |
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5 Unified Model, Conclusions, and Outlook |
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717 | (1) |
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718 | (5) |
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32 Histone y-H2AX Involvement in DNA Double-Strand Break Repair Pathways |
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723 | (14) |
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723 | (1) |
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2 Formation and Detection of γ-Phosphorylation |
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724 | (2) |
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3 y-Phosphorylation of H2A(X) Spans Megabase-Long Domains in Chromatin |
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726 | (1) |
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4 Kinases Involved in γ-Phosphorylation of H2A(X) Histone Family |
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727 | (1) |
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5 Recruitment of Repair Factors to γ-Phosphorylated Chromatin |
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728 | (1) |
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6 Models and Speculations About the Biological Role of γ-H2AX Foci |
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729 | (3) |
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732 | (5) |
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33 DNA Strand-Break Recognition, Signaling, and Resolution: The Role of Poly(ADP-Ribose) Polymerases-1 and -2 |
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737 | (18) |
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Josiane Menissier-de Murcia |
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737 | (1) |
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737 | (2) |
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3 Nick Sensor Function of PARP-1 |
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739 | (4) |
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4 Dual Role of DNA-Damage Induced PAR Synthesis: Break Signaling and Recruitment of XRCC1 |
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743 | (4) |
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5 No Cross-Talk Between PAR Synthesis and γ-H2AX Formation in Response to DNA-Strand Break Injury |
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747 | (2) |
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6 Conclusions and Future Prospects |
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749 | (1) |
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750 | (5) |
| Part VII. Perception Of DNA Damage For Initiating Regulatory Responses |
|
755 | (86) |
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34 Cellular and Molecular Responses to Alkylation Damage in DNA |
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757 | (24) |
|
|
|
|
|
|
|
757 | (3) |
|
2 The E. coli Adaptive Response: Translating Methyl DNA Adducts into a Transcriptional Signal |
|
|
760 | (6) |
|
3 Cellular Responses to O6MeG |
|
|
766 | (5) |
|
4 Cellular Responses to 3MeA |
|
|
771 | (4) |
|
5 Genome-Wide Analysis of Responses to Alkylating Agents |
|
|
775 | (1) |
|
|
|
776 | (1) |
|
|
|
776 | (5) |
|
35 Damage Signals Triggering the Escherichia coli SOS Response |
|
|
781 | (22) |
|
|
|
|
|
781 | (1) |
|
2 The E. coli SOS Response |
|
|
781 | (3) |
|
3 Structure-Function of the LexA Protein Family |
|
|
784 | (2) |
|
4 RecA Protein-DNA Interactions and LexA Self-Cleavage |
|
|
786 | (3) |
|
5 Role of DNA Damage in Inducing the E. coli SOS Response |
|
|
789 | (2) |
|
6 Upregulation of DNA Repair and DNA Damage Tolerance Under the SOS Response |
|
|
791 | (4) |
|
7 After the Damage is Repaired: Turning off the SOS Response and the Return to Normalcy |
|
|
795 | (2) |
|
8 Concluding Remarks and Future Perspectives |
|
|
797 | (1) |
|
|
|
798 | (5) |
|
36 Recognition of DNA Damage as the Initial Step of Eukaryotic Checkpoint Arrest |
|
|
803 | (24) |
|
|
|
|
|
803 | (1) |
|
2 Early Studies Characterizing Checkpoint Triggering Damage and Sensor Proteins |
|
|
804 | (1) |
|
3 The ATM Protein is a Kinase and a Putative Damage Sensor |
|
|
805 | (2) |
|
4 The ATR Protein and its Targeting Subunit |
|
|
807 | (1) |
|
5 PCNA- and RFC-like Clamp and Clamp Loader Complexes Function as Damage Sensors |
|
|
808 | (2) |
|
6 Crosstalk Between Sensors |
|
|
810 | (1) |
|
7 The MRN Complex Plays a Role in Checkpoint Arrests |
|
|
811 | (1) |
|
8 Synopsis: Independent But Communicating Sensors Are Linked By Common Requirements |
|
|
812 | (1) |
|
9 The Generation of a Transducible Signal |
|
|
812 | (2) |
|
10 Other Sensor Candidates |
|
|
814 | (1) |
|
|
|
815 | (1) |
|
12 Adaptation and Cell Cycle Restart |
|
|
816 | (2) |
|
|
|
818 | (9) |
|
37 Responses to Replication of DNA Damage |
|
|
827 | (14) |
|
|
|
|
|
|
|
827 | (1) |
|
2 How do Cells Deal with a Damaged Template During DNA Replication? |
|
|
828 | (2) |
|
|
|
830 | (7) |
|
4 Replication-Related Genome Instability |
|
|
837 | (1) |
|
|
|
837 | (4) |
| Index |
|
841 | |