brief contents Prologue xv Preface xvii CHAPTER 1 Welcome to Molecular B iology! 3 PART 1 The Structure of Proteins, Nucleic Acids, and Macromolecular Complexes 21 CHAPTER 2 Macromolecules 23 CHAPTER 3 Nucleic Acids 39 CHAPTER 4 The Physical Structure of Protein Molecules 67 CHAPTER 5 Macrom olecular Interactions and the Structure of Complex Aggregates 87 CHAPTER 6 The Genetic Material 109 CHAPTER 7 DNA Replication 131 CHAPTER 8 Transcription 163 CHAPTER 9 Translation 187 CHAPTER 10 Mutations, Mutagenesis, and DNA Repair 213 CHAPTER 11 Regulation of Gene Activity in Prokaryotes 251 CHAPTER 12 Bacteriophage 281 CHAPTER 13 Regulation of Gene Activity in Eukaryotes 311 CHAPTER 14 Plasmids and Transposons 351 CHAPTER 15 Recom binant DNA and Genetic Engineering: Molecular Tailoring of Genes 381 CHAPTER 16 Molecular Biology Is Expanding Its Reach 409 APPENDIX Chemical Principles Important for Understanding Molecular Biology 442 List of Essential Concepts of Molecular Biology 471 Glossary 475 References for Further Reading 491 Answers to Questions and Problems 497 Index 515 contents Prologue xv Preface xvii CHAPTER 1 Welcome to Molecular Biology! GEORGE M.MALACINSKI 3 Goals of Molecular Biology 3 The Early Years4 Model Biological Systems 5 Methodology of Molecular Biology 9 Rapid Progress in Molecular Biology 12 Putting the Details of Molecular Biology in Perspective 14 Concepts of Molecular Biology 16 Progression Diagram 17 Rewards from Studying Molecular Biology 17 PART I The Structure of Proteins, Nucleic Acids, and Macromolecular Complexes 21 CHAPTER 2 Macromolecules GEORGE M.MALACINSKI 23 Chemical Structures of the Major Classes of Macromolecules24 Noncovalent Interactions that Determine the Three-dimensional Strnrtnrac of Prntainc and Nnrleic Acids 28 Macromolecule Isolation and Characterization 31 CHAPTER 3 Nucleic Acids ROBERT CEDERGREN 39 Physical and Chemical Structure of DNA 40 Alternate DNA Structures 43 Circular and Superhelical DNA 45 Renaturation 50 Hybridization 53 The Structure of RNA 55 Hydrolysis of Nucleic Acids 56 Sequencing Nucleic Acids 58 Synthesis of DNA 60 A Future Practical Application? 62 CHAPTER 4 The Physical Scture of Protein Molecules ALEXANDRA CYNTHIA NEwToe 61 Basic Features of Protein Molecules 68 The Folding of a Polypeptide Chain 68 The a Helix and Structures 70 Protein Structure 73 Proteins with Subunits 76 Enzymes 79 A Future Application 82 CHAPTER 5 Macromolecular Interactions and the Structure of Complex Aggregates GEORGE M. MALACINSKI 87 A Complex DNA Structure: The E. Coli Chromosome 88 Chromosomes and Chromatin 91 Interaction of DNA and Proteins that Recognize a Specific Base Sequence 96 Biological Membranes 99 Cytoskeletal Elements 102 AFuture Practical Application? 103 PART II Function of Macromolecules 107 CHAPTER 6 The Genetic Material ROBERT L. SINSHEIMER 109 Early Observations on the Mechanism of Heredity 110 Identification of DNA as the Genetic Material 112 Identification of RNA as the Genetic Material of Certain Viruses 120 Properties of the Genetic Material 121 RNA as the Genetir Material 127 CHAPTER 7 DNA Replication_KENNETH MARIANS 131 Semiconservative Replication of Double-Stranded DNA 132 Untwisting of Highly Coiled DNA Is Required for DNA Replication 133 Initiation of DNA Replication 136 Unwinding of DNA for Replication 139 Elongation of Newly Synthesized Strands 140 DNA Polymerase III Consists of Multiple Subunits 143 Antiparallel DNA Strands and Discontinuous Replication 145 The Complete DNA Replication System 152 Replication of Eukaryotic Chromosomes 156 A Future Practical Avvlication? 158 CHAPTE 8 Transcription Jonn RICHARDSON 163 Enzymatic Synthesis of RNA 164 Transcription Signals 166 Classes of RNA Molecules 171 Transcription in Eukaryotes 174 Means of Studying Intracellular RNA 180 A Future Practical Avolication? 182 CHAPTER 9 Translation JOSEPH LAN 187 Outline of Translation 188 The Genetic Code 189 The Wobble Hypothesis 194 Polycistronic mRNA196 Overlapping Genes 196 Polypeptide Synthesis 198 Stages of Polypeptide Synthesis in Prokaryotes 200 Complex Translation Units 204 Antibiotics 208 A Future Practical Avvlication? 208 CHAPTER 10 Mutations, Mutagenesis, and DNA Repair PHILIP C. HANAWALT 213 Types of Mutations 214 Biochemical Basis of Mutants 216 Mutagenesis 218 Spontaneous Mutations and Their Repair 220 Induced Mutations 223 Reversion 229 Reversion as a Means of Detecting Mutagens and Carcinogens 234 DNA Repair Mechanisms 236 Repair by Direct Reversal 236 Excision-Repair 237 Recombinational Repair 238 The SOS Response 240 Future Practical Applications? 243 PART III Coordination of Macromolecular Function in Cells 249 CHAPTER 11 Regulation of Gene Activity in Prokaryotes SANKAR L.ADHYA 251 Principles of Regulation 252 Transcriptional Regulation 253 Post-Transcriptional Control 272 Feedback Inhibition and Allosteric Control 274 A Future Practical Application? 276 CHAPTER 12 Bacteriophage DAVID PARMA AND LARRY GOLD 281 Stages in the Lytic Life Cycle of a Typical Phage 283 Specific Phage 286 Transducing Phage304 A Future Practical Application? 307 CHAPTER 13 Regulation of Gene Activity in Eukaryotes HANS-PETER MULLER AND WALTER SCHAFFNER 311 Important Differences in the Genetic Organization of Prokaryotes and Eukaryotes 312 The Regulation of Transcription Initiation 313 The Regulation of RNA Processing 324 Regulation of Nucleocytoplasmic mRNA Transport 330 Regulation of mRNA Stability 331 Regulation of Translation 334 Regulation of Protein Activity 335 Gene Rearrangement:Joining of Coding Sequences in the Immune System 340 A Future Practical Application? 344 PART IV Experimental Manipulation of Macomolecules 349 CHAPTER 14 Plasmids and Transposons BARRY POLISKY 351 Plasmid-Borne Genes 353 Plasmid Transfer 354 Plasmid DNA Replication 361 Transposable Elements 364 Transposable Elements in Eukaryotes 374 A Future Practical Application? 375 CHAPTER 15 Recombinant DNA and Genetic Engineering: Molecular Tailoring of Genes DOROTHY M.SKINNER AND CHRISTIE A.HOLLAND 381 Plasmids Act as Nature's Interlopers 382 Restriction Enzymes Function as Nature's Pinking Shears 382 Genetic Interlopers:Vectors Function as Vehicles for Transferring Genes 392 Detection of Recombinant DNA Molecules 399 Applications of Genetic Engineering 403 CHAPTER 16 Molecular Biology IS Expanding ITS Reach PAMELA L.HANRATTY 409 Uses of Recombinant DNA Technology in Research 410 Uses of Recombinant DNA Technology in Medicine 417 Uses of Recombinant DNA Technology in Agriculture 427 Other Commercial and Industrial Applications 430 Molecular Biology: On the Front Line of the Battle Against AIDS 431 Social and Ethical Issues 433 APPENDIX Chemical Principles Important for Undestanding Molecular Biology JUDITH A.JAEHNING 443 Structure of the Atom 444 Chemical Bonds 444 The Ionization of Water-The pH Scale 450 Organic Chemistry 453 Concluding Note 469 List of Essential Concepts 471 Glossary 475 References for Further Reading 491 Answers to Questions and Problems 497 Index 515