Animal cell DNA polymerases

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Hauptverfasser: Fry, Michael (VerfasserIn), Loeb, Lawrence A. (VerfasserIn)
Format: Buch
Sprache:English
Veröffentlicht: Boca Raton, Fla. CRC Press 1986
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adam_text Animal Cell DNA Polymerases Authors Michael Fry, Ph D Associate Professor Unit of Biochemistry Faculty of Medicine Technion-Israel Institute of Technology Haifa, Israel Lawrence A Loeb, MD, Ph D Professor and Director The Joseph Gottstein Memorial Cancer Research Laboratory Department of Pathology University of Washington Seattle, Washington CRC Press, Inc Boca Raton, Florida TABLE OF CONTENTS Chapter I General Introduction 1 Chapter 2 Multiplicity of DNA Polymerases in Animal Cells 3 I Basic Enzymological Characteristics of DNA Polymerases 3 II Multiplicity of DNA Polymerases in Animal Cells — A Brief Historical Perspective 4 III Defining Criteria for Classification of Animal Cell DNA Polymerases 8 IV Roles of DNA Polymerases-a, -P, and -y in DNA Replication and Repair 8 References 10 Chapter 3 DNA Polymerase-a 13 I Introductory Remarks 13 II Structure of Polymerase-^ 14 A Enzyme Purification Methods 14 B Size of the Catalytic Core Subunit 15 C Calf Thymus DNA Polymerase-a 15 D Rat Liver 18 E Chick Embryo 19 F Drosophila 19 G Xenopus laevis 20 H Bone Marrow 20 I Mouse Myeloma 20 J Cultured Human Cells 21 III Is Polymerase-a Modified Posttranslationally? 25 IV Auxiliary Activities Associated with DNA Polymerase-a 26 A Exonuclease 26 B DNA Primase 26 1 Structural Relationships Between Primase and a-Polymerase 26 27- Major Enzymic Properties of DNA Primase 30 C Primer-Template Recognition Proteins 33 1 Helix Destabilizing Proteins 33 2 Primer Recognition Protein Factors 34 3 DNA Binding Proteins 35 4 Other Proteins Which Affect a-Polymerase 36 D Polymerase-a and Diadenosine-5 ,5 -P P4-tetraphosphate-Binding Proteins 37 V Catalytic Properties of DNA Polymerase-a 39 A Interaction of Polymerase-a with the Template 40 B Interaction of Polymerase-a with the Primer Stem 41 C Interaction of Polymerase-a with Metal Activators 42 D Nucleotide Substrates for DNA Polymerase-a 42 E The Initial Ordered Interaction of Polymerase-a with Its Reactants 43 F Elongation by DNA Polymerase-a 44 1 Processivity 44 2 Barriers to DNA Elongation 46 G Gap-Filling and Long-Stretch DNA Synthesis by a-Polymerase 47 VI Selective Inhibitors of DNA Polymerase-a 48 A Sulfhydryl Group Reactive Reagents 48 B Aphidicolin 49 C 6-(Arylamino)uracils and NJ-arylaminopurines 52 D Arabinose Analogs of Deoxynucleotides 53 E Phosphonacetic Acid 54 F 9-(2-Hydroxyethoxymethyl)guanine (Acyclovir) and 2 -Nor-2 -deoxy- guanosine (2 -NDG) 55 G Novobiocin 55 H Hemin 55 I Plant Cell Agglutinins 55 J Modified DNA Templates 55 K 2 -3 -Dideoxythymide-5 -triphosphate 56 L Palmitoyl Coenzyme A 56 M /}-Lapachone 56 N Other Inhibitors 56 VII Update 57 A Structure of DNA Polymerase-a 57 B Auxiliary Activities Associated with DNA Polymerase-a 57 1 DNA Primase 57 a Structural Aspects 57 b Catalytic Aspects 58 2 DNA Binding Proteins 59 C Chromososmal Localization of the Human DNA Polymerase-a Gene 59 References 60 Chapter 4 DNA Polymerase-/} 75 I Introductory Remarks 75 II Structure of Polymerase-/} 76 III Proteins Auxiliary to DNA Polymerase-/? 77 A DNase V 78 B ATPase Trr 78 C DNA Binding Proteins 7 79 IV Catalytic Properties of DNA Polymerase-/} 79 A Interaction of DNA Polymerase-/} with Primer-Template 79 B Primer-Template Binding and Divalent Metal Ion Requirement 80 C Template DNA Gap Size Preference of DNA Polymerase-/} 81 D The Ordered Initial Interaction of Polymerase-/} with Template- Primer and Nucleotide Substrates 81 E Processivity of DNA Synthesis Catalyzed by Polymerase-/} 82 V Inhibitors of DNA Polymerase-/} Activity 82 A Sulfhydryl Group Reactive Agents 82 B Inorganic Phosphate 83 C 2 ,3 -Dideoxynucleoside-5-triphosphates 83 D Other Inhibitors 84 E Preferential Sensitivity of DNA Polymerase-/} to Heat Activation 84 VI Update 85 A Chromosomal Localization of Human DNA Polymerase-/} Gene 85 References 85 Chapter 5 DNA Polymerase-y and DNA Polymerase-6 91 I DNA Polymerase-y 91 A Structure 92 B Catalytic Properties 93 1 Primer-Template Utilization 93 2 Processivity and Long-Stretch DNA Synthesis 94 C Inhibitors 95 1 Sulfhydryl Group Reactive Agents 95 2 2 ,3 -Dideoxythymidine-5-triphosphate 95 3 Intercalating Agents 95 4 Other Inhibitors 95 II DNA Polymerase-^ 96 A Structure 96 B The Association Between Polymerase-cJ and 3 —5 -Exonuclease 97 C Open Questions Concerning DNA Polymerase-6 98 References 98 Chapter 6 Roles of Animal Cell DNA Polymerases in Replication of Cellular DNA 103 I Introductory Remarks 103 II Replication of Nuclear DNA 104 A Participation of Polymerase-a in Nuclear DNA Replication 104 1 Intracellular Localization of DNA Polymerases 104 a Association of DNA Polymerases-a, -/?, and -y with the Cell Nucleus 105 (1) DNA Polymerase-a 105 (2) DNA Polymerase-/? 108 (3) DNA Polymerase-y 108 b Association of Polymerase-a with the Nuclear Matrix 109 2 Intracellular Levels of DNA Polymerases During Cell Cycling 110 a Evidence with Postmitotic Cells Ill b Studies on Quiescent Cells Stimulated to Divide Ill c Studies with Synchronized Cultured Cells 114 3 DNA Replication in Cell Mutants with Modified DNA Polymerase-a 114 4 Is DNA Polymerase-a a Component of a Multienzyme Replicative Complex? 115 B Participation of Polymerase-a in Genomic DNA Replication — Studies with Selective Inhibitors 118 1 Studies with Intact Cells 118 2 Studies with Isolated Replicative Systems 118 3 Probing DNA Replication with Monospecific Antibodies Against Polymerase-a 120 C Correlating Enzymic Properties of Polymerase-a, -/?, and -y to Properties Required of a Replicative DNA Polymerase 120 1 Relationship Between Unique Catalytic Properties of Polymerases-a, -/?, and -y and Properties Required of a Replicative DNA Polymerase 120 a Processivity 120 b Interaction with Template DNA 121 c Interaction with Primer 121 d Gap-Filling and Long-Stretch DNA Synthesis 121 e Summary 122 2 Association of Polymerase-a with Auxiliary Protein 122 III Replication of Mitochondrial DNA by DNA Polymerase-y 123 A Compartmentalization of Polymerase-y in Mitochondria 123 B Participation of Polymerase-y in Synthesis of Mitochondrial DNA Studies on the Effect of Selective Inhibitors and on Catalytic Properties 123 IV Concluding Remarks 124 V Update 125 A Association of Polymerase-a with the Nuclear Matrix 125 B Intracellular Levels of DNA Polymerases During Cell Cycling 126 C DNA Replication in Cell Mutants with Modified DNA Polymerase-a 126 D Is DNA Polymerase-a a Component of a Multienzyme Replicative Complex? 126 References 127 Chapter 7 Roles of Animal Cell DNA Polymerases in DNA Repair Synthesis 135 I Introductory Remarks 135 II Physiology of DNA Polymerases-a and -/} in Cells Containing Damaged DNA 136 A Postmitotic Cells 136 B Cycling Cells 137 III Studies on Mutant Cells with Deficient Repair or Modified DNA Polymerase-a 138 A Hereditary Diseases of Defective DNA Repair 138 B Mutant Cell with a Modified DNA Polymerase-a 139 IV Involvement of Polymerase-a and -p in Repair: Studies with Selective Inhibitors „ 140 A Evidence for the Participation of Polymerase-a in Repair Synthesis 140 1 Early Observations 140 2 Cell Type Variance in Response of Repair to Aphidicolin 141 3 Further Evidence for the Function of Polymerase-a in Repair Synthesis 142 4 Role of Polymerase-a in Repair of Damage Caused by Different Agents 142 5 Effect of the Extent of Damage on Mobilization of Polymerases for Repair Synthesis 143 6 Effect on Damaged DNA of the Arrest of Polymerase-a Activity 144 B DNA Polymerase-/} 145 V Enzymatic Properties of DNA Polymerases and Their Concordance with Roles in DNA Repair 147 A Catalytic Properties of DNA Polymerases-a and -(J 147 B In Vitro Utilization of Damaged DNA Templates by Polymerases-a and -P 147 C Accessory Proteins for DNA Polymerases and the Hypothetical Multienzyme Repair Complex 148 VI Reconstructed in Vitro Model Systems for Repair of Damaged DNA 149 VII Concluding Remarks 151 VIII Update 151 A Involvement of DNA Polymerases-a and -/} in Repair Synthesis: Studies with Selective Inhibitors 151 References 152 Chapter 8 Fidelity of DNA Synthesis 157 I Introductory Remarks 157 II Methods to Measure the Fidelity of DNA Synthesis 158 A Studies with Synthetic Polynucleotide Templates 158 B Reversion Assays with Mutant DNA Templates 159 III Fidelity of DNA Polymerase-a 162 A Studies with Synthetic Polynucleotides 162 B Studies with Natural DNA Template 163 C Associated Proteins and Other Factors 165 IV Fidelity of DNA Polymerase-/} 166 A Studies with Synthetic Polynucleotide Templates 167 B Studies with Natural DNA Templates 168 C Associated Factors 169 V Fidelity of DNA Polymerase-y and -6 169 VI Mechanism for Enhanced Fidelity by Animal DNA Polymerases 170 A The K„ Discrimination Model 171 B Conformation Model 171 C Energy Relay 172 D Pyrophosphate-Mediated Proofreading 172 VII Mechanisms for Accuracy in Animal Cells 173 A Proofreading in Animal Cells 173 B Mismatch Correction in Animal Cell 174 VIII Mutagenesis by DNA Polymerases 174 A Nucleotide Pools 175 B Incorporation of Nucleotide Analogs 175 C Effect of Mutagenic Metal Ions 176 D Template Modifications 176 E Alterations in DNA Polymerases 177 F SOS Repair in Animal Cells 177 IX Update 178 A Mutational Spectra 178 1 DNA Polymerase-a 178 2 DNA Polymerase-/} 178 3 Relationship of Fidelity to Processivity 178 References 178 Chapter 9 Biology of Animal Cell DNA Polymerases 185 I Evolution of DNA Polymerases 185 A DNA Polymerase-a 185 B DNA Polymerase-/} 186 C DNA Polymerase-y 187 II DNA Polymerases in Development 188 A Differentiation 188 B Embryogenesis and Development 189 III DNA Polymerases in Aging 191 A Diminishing Cell Proliferation During Aging and Activities of DNA Polymerases 191 B Fidelity of DNA Polymerases in Aging Cells 193 IV Update 194 A Evolution of DNA Polymerase-/} 194 B DNA Polymerase Activities in Aging Cells 195 References 196 Chapter 10 Future Pespectives 201 I Introduction 201 II Structural Analysis of DNA Polymerases 201 III Physiological Variation in the Level of a-Polymerase, Molecular Microheterogeneity, and Proteolysis 203 IV The Nature of the Replicative Complex 204 V Fidelity of DNA Replication 205 VI Roles of DNA Polymerases in DNA Repair Synthesis and Their Possible Inclusion in Multiprotein Repair Complexes 206 VII Function of DNA Polymerase-y in the Cell Nucleus 206 VIII Distribution, Properties, and Function of DNA Polymerase-6 207 IX Function of DNA Polymerases in DNA Recombination 207 X Conclusion 208 References 208 Index 209
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spellingShingle Fry, Michael
Loeb, Lawrence A.
Animal cell DNA polymerases
DNA polymerases
DNA-Directed DNA Polymerase
title Animal cell DNA polymerases
title_auth Animal cell DNA polymerases
title_exact_search Animal cell DNA polymerases
title_full Animal cell DNA polymerases Michael Fry and Lawrence A. Loeb
title_fullStr Animal cell DNA polymerases Michael Fry and Lawrence A. Loeb
title_full_unstemmed Animal cell DNA polymerases Michael Fry and Lawrence A. Loeb
title_short Animal cell DNA polymerases
title_sort animal cell dna polymerases
topic DNA polymerases
DNA-Directed DNA Polymerase
topic_facet DNA polymerases
DNA-Directed DNA Polymerase
url http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005341978&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
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