LEWIN'S GENES XIIPDF格式文档图书下载

PART Ⅰ Genes and Chromosomes 1

Chapter 1 Genes Are DNA and Encode RNAs and Polypeptides&Edited by Esther Siegfried 2

1.1 Introduction 3

1.2 DNA Is the Genetic Material of Bacteria and Viruses 4

1.3 DNA Is the Genetic Material of Eukaryotic Cells 6

1.4 Polynucleotide Chains Have Nitrogenous Bases Linked to a Sugar-Phosphate Backbone 6

1.5 Supercoiling Affects the Structure of DNA 7

1.6 DNA Is a Double Helix 9

1.7 DNA Replication Is Semiconservative 11

1.8 Polymerases Act on Separated DNA Strands at the Replication Fork 12

1.9 Genetic Information Can Be Provided by DNA or RNA 13

1.10 Nucleic Acids Hybridize by Base Pairing 15

1.11 Mutations Change the Sequence of DNA 16

1.12 Mutations Can Affect Single Base Pairs or Longer Sequences 17

1.13 The Effects of Mutations Can Be Reversed 18

1.14 Mutations Are Concentrated at Hotspots 19

1.15 Many Hotspots Result from Modified Bases 19

1.16 Some Hereditary Agents Are Extremely Small 20

1.17 Most Genes Encode Polypeptides 21

1.18 Mutations in the Same Gene Cannot Complement 22

1.19 Mutations May Cause Loss of Function or Gain of Function 23

1.20 A Locus Can Have Many Different Mutant Alleles 24

1.21 A Locus Can Have More Than One Wild-Type Allele 25

1.22 Recombination Occurs by Physical Exchange of DNA 25

1.23 The Genetic Code Is Triplet 27

1.24 Every Coding Sequence Has Three Possible Reading Frames 29

1.25 Bacterial Genes Are Colinear with Their Products 29

1.26 Several Processes Are Required to Express the Product of a Gene 30

1.27 Proteins Are trans-Acting but Sites on DNAArecis-Acting 31

Chapter 2 Methods in Molecular Biology and Genetic Engineering 35

2.1Introduction 35

2.2 Nucleases 36

2.3Cloning 38

2.4 Cloning Vectors Can Be Specialized for Different Purposes 40

2.5 Nucleic Acid Detection 43

2.6 DNA Separation Techniques 45

2.7 DNA Sequencing 48

2.8 PCR and RT-PCR 50

2.9 Blotting Methods 55

2.10 DNA Microarrays 58

2.11 Chromatin Immunoprecipitation 61

2.12 Gene Knockouts，Transgenics，and Genome Editing 62

Chapter 3 The Interrupted Gene 71

3.1 Introduction 71

3.2 An Interrupted Gene Has Exons and Introns 72

3.3 Exon and Intron Base Compositions Differ 73

3.4 Organization of Interrupted Genes Can Be Conserved 73

3.5 Exon Sequences Under Negative Selection Are Conserved but Introns Vary 74

3.6 Exon Sequences Under Positive Selection Vary but Introns Are Conserved 75

3.7 Genes Show a Wide Distribution of Sizes Due Primarily to Intron Size and Number Variation 76

3.8 Some DNA Sequences Encode More Than One Polypeptide 78

3.9 Some Exons Correspond to Protein Functional Domains 79

3.10 Members of a Gene Family Have a Common Organization 81

3.11 There Are Many Forms of Information in DNA 82

Chapter 4 The Content of the Genome 87

4.1 Introduction 87

4.2 Genome Mapping Reveals That Individual Genomes Show Extensive Variation 88

4.3 SNPs Can Be Associated with Genetic Disorders 89

4.4 Eukaryotic Genomes Contain Nonrepetitive and Repetitive DNA Sequences 90

4.5 Eukaryotic Protein-Coding Genes Can Be Identified by the Conservation of Exons and of Genome Organization 92

4.6 Some Eukaryotic Organelles Have DNA 94

4.7 Organelle Genomes Are Circular DNAs That Encode Organelle Proteins 95

4.8 The Chloroplast Genome Encodes Many Proteins and RNAs 97

4.9 Mitochondria and Chloroplasts Evolved by Endosymbiosis 98

Chapter 5 Genome Sequences and Evolution 101

5.1 Introduction 102

5.2 Prokaryotic Gene Numbers Range Over an Order of Magnitude 103

5.3 Total Gene Number Is Known for Several Eukaryotes 104

5.4 How Many Different Types of Genes Are There？ 106

5.5 The Human Genome Has Fewer Genes Than Originally Expected 108

5.6 How Are Genes and Other Sequences Distributed in the Genome？ 110

5.7 The Y Chromosome Has Several Male-Specific Genes 111

5.8 How Many Genes Are Essential？ 112

5.9 About 10，000 Genes Are Expressed at Widely Differing Levels in a Eukaryotic Cell 115

5.10 Expressed Gene Number Can Be Measured En Masse 116

5.11 DNA Sequences Evolve by Mutation and a Sorting Mechanism 117

5.12 Selection Can Be Detected by Measuring Sequence Variation 119

5.13 A Constant Rate of Sequence Divergence Is a Molecular Clock 122

5.14 The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences 125

5.15 How Did Interrupted Genes Evolve？ 126

5.16 Why Are Some Genomes So Large？ 128

5.17 Morphological Complexity Evolves by Adding New Gene Functions 130

5.18 Gene Duplication Contributes to Genome Evolution 131

5.19 Globin Clusters Arise by Duplication and Divergence 132

5.20 Pseudogenes Have Lost Their Original Functions 134

5.21 Genome Duplication Has Played a Role in Plant and Vertebrate Evolution 135

5.22 What Is the Role of Transposable Elements in Genome Evolution 137

5.23 There Can Be Biases in Mutation，Gene Conversion，and Codon Usage 137

Chapter 6 Clusters and Repeats 143

6.1 Introduction 143

6.2 Unequal Crossing-Over Rearranges Gene Clusters 145

6.3 Genes for rRNA Form Tandem Repeats Including an Invariant Transcription Unit 147

6.4 Crossover Fixation Could Maintain Identical Repeats 150

6.5 Satellite DNAs Often Lie in Heterochromatin 152

6.6 Arthropod Satellites Have Very Short Identical Repeats 153

6.7 Mammalian Satellites Consist of Hierarchical Repeats 154

6.8 Minisatellites Are Useful for DNA Profiling 157

Chapter 7 Chromosomes&Edited by Hank W.Bass 161

7.1 Introduction 162

7.2 Viral Genomes Are Packaged into Their Coats 163

7.3 The Bacterial Genome Is a Nucleoid with Dynamic Structural Properties 165

7.4 The Bacterial Genome Is Supercoiled and Has Four Macrodomains 167

7.5 Eukaryotic DNA Has Loops and Domains Attached to a Scaffold 168

7.6 Specific Sequences Attach DNA to an Interphase Matrix 169

7.7 Chromatin Is Divided into Euchromatin and Heterochromatin 170

7.8 Chromosomes Have Banding Patterns 172

7.9 Lampbrush Chromosomes Are Extended 173

7.10 Polytene Chromosomes Form Bands 174

7.11 Polytene Chromosomes Expand at Sites of Gene Expression 175

7.12 The Eukaryotic Chromosome Is a Segregation Device 176

7.13 Regional Centromeres Contain a Centromeric Histone H3 Variant and Repetitive DNA 177

7.14 Point Centromeres in S.cerevisiae Contain Short，Essential DNA Sequences 179

7.15 The S.cerevisiae Centromere Binds a Protein Complex 179

7.16 Telomeres Have Simple Repeating Sequences 180

7.17 Telomeres Seal the Chromosome Ends and Function in Meiotic Chromosome Pairing 181

7.18 Telomeres Are Synthesized by a Ribonucleoprotein Enzyme 182

7.19 Telomeres Are Essential for Survival 184

Chapter 8 Chromatin&Edited by Craig Peterson 189

8.1 Introduction 189

8.2 DNA Is Organized in Arrays of Nucleosomes 190

8.3 The Nucleosome Is the Subunit of All Chromatin 192

8.4 Nucleosomes Are Covalently Modified 196

8.5 Histone Variants Produce Alternative Nucleosomes 199

8.6 DNA Structure Varies on the Nucleosomal Surface 202

8.7 The Path of Nucleosomes in the Chromatin Fiber 205

8.8 Replication of Chromatin Requires Assembly of Nucleosomes 207

8.9 Do Nucleosomes Lie at Specific Positions？ 209

8.10 Nucleosomes Are Displaced and Reassembled During Transcription 212

8.11 DNase Sensitivity Detects Changes in Chromatin Structure 215

8.12 An LCR Can Control a Domain 217

8.13 Insulators Define Transcriptionally Independent Domains 218

PARTⅡ DNA Replication and Recombination 227

Chapter 9 Replication Is Connected to the Cell Cycle&Edited by Barbara Funnell 228

9.1 Introduction 228

9.2 Bacterial Replication Is Connected to the Cell Cycle 230

9.3 The Shape and Spatial Organization of a Bacterium Are Important During Chromosome Segregation and Cell Division 231

9.4 Mutations in Division or Segregation Affect Cell Shape 232

9.5 FtsZ Is Necessary for Septum Formation 233

9.6 min and noc/slm Genes Regulate the Location of the Septum 233

9.7 Partition Involves Separation of the Chromosomes 234

9.8 Chromosomal Segregation Might Require Site-Specific Recombination 235

9.9 The Eukaryotic Growth Factor Signal Transduction Pathway Promotes Entry to S Phase 237

9.10 Checkpoint Control for Entry into S Phase：p53，a Guardian of the Checkpoint 239

9.11 Checkpoint Control for Entry into S Phase：Rb，a Guardian of the Checkpoint 240

Chapter 10 The Replicon：Initiation of Replication 245

10.1 Introduction 245

10.2 An Origin Usually Initiates Bidirectional Replication 246

10.3 The Bacterial Genome Is （Usually） a Single Circular Replicon 247

10.4 Methylation of the Bacterial Origin Regulates Initiation 248

10.5 Initiation：Creating the Replication Forks at the Origin oriC 249

10.6 Multiple Mechanisms Exist to Prevent Premature Reinitiation of Replication 251

10.7 Archaeal Chromosomes Can Contain Multiple Replicons 252

10.8 Each Eukaryotic Chromosome Contains Many Replicons 252

10.9 Replication Origins Can Be Isolated in Yeast 253

10.10 Licensing Factor Controls Eukaryotic Rereplication 255

10.11 Licensing Factor Binds to ORC 256

Chapter 11 DNA Replication 261

11.1 Introduction 261

11.2 DNA Polymerases Are the Enzymes That Make DNA 262

11.3 DNA Polymerases Have Various Nuclease Activities 264

11.4 DNA Polymerases Control the Fidelity of Replication 264

11.5 DNA Polymerases Have a Common Structure 265

11.6 The Two New DNA Strands Have Different Modes of Synthesis 266

11.7 Replication Requires a Helicase and a Single-Stranded Binding Protein 267

11.8 Priming Is Required to Start DNA Synthesis 268

11.9 Coordinating Synthesis of the Lagging and Leading Strands 270

11.10 DNA Polymerase Holoenzyme Consists of Subcomplexes 270

11.11 The Clamp Controls Association of Core Enzyme with DNA 271

11.12 Okazaki Fragments Are Linked by Ligase 274

11.13 Separate Eukaryotic DNA Polymerases Undertake Initiation and Elongation 276

11.14 Lesion Bypass Requires Polymerase Replacement 278

11.15 Termination of Replication 279

Chapter 12 Extrachromosomal Replicons 283

12.1 Introduction 283

12.2 The Ends of Linear DNA Are a Problem for Replication 284

12.3 Terminal Proteins Enable Initiation at the Ends of Viral DNAs 285

12.4 Rolling Circles Produce Multimers of a Replicon 286

12.5 Rolling Circles Are Used to Replicate Phage Genomes 287

12.6 The F Plasmid Is Transferred by Conjugation Between Bacteria 288

12.7 Conjugation Transfers Single-Stranded DNA 290

12.8 Single-Copy Plasmids Have a Partitioning System 291

12.9 Plasmid Incompatibility Is Determined by the Replicon 293

12.10 The ColE1 Compatibility System Is Controlled by an RNA Regulator 293

12.11 How Do Mitochondria Replicate and Segregate？ 296

12.12 D Loops Maintain Mitochondrial Origins 297

12.13 The Bacterial Ti Plasmid Causes Crown Gall Disease in Plants 298

12.14 T-DNA Carries Genes Required for Infection 299

12.15 Transfer of T- DNA Resembles Bacterial Conjugation 301

Chapter 13 Homologous and Site-Specific Recombination&Edited by Hannah L.Klein and Samantha Hoot 305

13.1 Introduction 306

13.2 Homologous Recombination Occurs Between Synapsed Chromosomes in Meiosis 306

13.3 Double-Strand Breaks Initiate Recombination 308

13.4 Gene Conversion Accounts for Interallelic Recombination 310

13.5 The Synthesis-Dependent Strand-Annealing Model 311

13.6 The Single-Strand Annealing Mechanism Functions at Some Double-Strand Breaks 312

13.7 Break-Induced Replication Can Repair Double-Strand Breaks 313

13.8 Recombining Meiotic Chromosomes Are Connected by the Synaptonemal Complex 314

13.9 The Synaptonemal Complex Forms After Double-Strand Breaks 315

13.10 Pairing and Synaptonemal Complex Formation Are Independent 316

13.11 The Bacterial RecBCD System Is Stimulated by chi Sequences 317

13.12 Strand-Transfer Proteins Catalyze Single-Strand Assimilation 318

13.13 Holliday Junctions Must Be Resolved 321

13.14 Eukaryotic Genes Involved in Homologous Recombination 322

1.End Processing/Presynapsis 322

2.Synapsis 324

3.DNA Heteroduplex Extension and Branch Migration 324

4.Resolution 324

13.15 Specialized Recombination Involves Specific Sites 325

13.16 Site-Specific Recombination Involves Breakage and Reunion 326

13.17 Site-Specific Recombination Resembles Topoisomerase Activity 327

13.18 Lambda Recombination Occurs in an Intasome 328

13.19 Yeast Can Switch Silent and Active Mating-Type Loci 329

13.20 Unidirectional Gene Conversion Is Initiated by the Recipient MAT Locus 331

13.21 Antigenic Variation in Trypanosomes Uses Homologous Recombination 332

13.22 Recombination Pathways Adapted for Experimental Systems 332

Chapter 14 Repair Systems 339

14.1 Introduction 339

14.2 Repair Systems Correct Damage to DNA 341

14.3 Excision Repair Systems in E.coli 343

14.4 Eukaryotic Nucleotide Excision Repair Pathways 344

14.5 Base Excision Repair Systems Require Glycosylases 345

14.6 Error-Prone Repair and Translesion Synthesis 349

14.7 Controlling the Direction of Mismatch Repair 349

14.8 Recombination-Repair Systems in E.coli 352

14.9 Recombination Is an Important Mechanism to Recover from Replication Errors 353

14.10 Recombination-Repair of Double-Strand Breaks in Eukaryotes 354

14.11 Nonhomologous End Joining Also Repairs Double-Strand Breaks 356

14.12 DNA Repair in Eukaryotes Occurs in the Context of Chromatin 357

14.13 RecA Triggers the SOS System 361

Chapter 15 Transposable Elements and Retroviruses&Edited by Damon Lisch 367

15.1 Introduction 368

15.2 Insertion Sequences Are Simple Transposition Modules 369

15.3 Transposition Occurs by Both Replicative and Nonreplicative Mechanisms 370

15.4 Transposons Cause Rearrangement of DNA 372

15.5 Replicative Transposition Proceeds Through a Cointegrate 373

15.6 Nonreplicative Transposition Proceeds by Breakage and Reunion 374

15.7 Transposons Form Superfamilies and Families 375

15.8 The Role of Transposable Elements in Hybrid Dysgenesis 378

15.9 P Elements Are Activated in the Germline 379

15.10 The Retrovirus Life Cycle Involves Transposition-Like Events 381

15.11 Retroviral Genes Code for Polyproteins 381

15.12 Viral DNA Is Generated by Reverse Transcription 383

15.13 Viral DNA Integrates into the Chromosome 385

15.14 Retroviruses May Transduce Cellular Sequences 386

15.15 Retroelements Fall into Three Classes 388

15.16 Yeast Ty Elements Resemble Retroviruses 389

15.17 The Alu Family Has Many Widely Dispersed Members 391

15.18 LINEs Use an Endonuclease to Generate a Priming End 392

Chapter 16 Somatic DNA Recombination and Hypermutation in the Immune System&Edited by Paolo Casali 397

16.1 The Immune System：Innate and Adaptive Immunity 398

16.2 The Innate Response Utilizes Conserved Recognition Molecules and Signaling Pathways 399

16.3 Adaptive Immunity 401

16.4 Clonal Selection Amplifies Lymphocytes That Respond to a Given Antigen 402

16.5 Ig Genes Are Assembled from Discrete DNA Segments in B Lymphocytes 404

16.6 L Chains Are Assembled by a Single Recombination Event 405

16.7 H Chains Are Assembled by Two Sequential Recombination Events 406

16.8 Recombination Generates Extensive Diversity 407

16.9 V（D）J DNA Recombination Relies on RSS and Occurs by Deletion or Inversion 408

16.10 Allelic Exclusion Is Triggered by Productive Rearrangements 410

16.11 RAG1/RAG2 Catalyze Breakage and Religation of V（D）J Gene Segments 411

16.12 B Cell Development in the Bone Marrow：From Common Lymphoid Progenitor to Mature B Cell 413

16.13 Class Switch DNA Recombination 415

16.14 CSR Involves AID and Elements of the NHEJ Pathway 416

16.15 Somatic Hypermutation Generates Additional Diversity and Provides the Substrate for Higher-Affinity Submutants 418

16.16 SHM Is Mediated by AID，Ung，Elements of the Mismatch DNA Repair Machinery，and Translesion DNA Synthesis Polymerases 419

16.17 Igs Expressed in Avians Are Assembled from Pseudogenes 420

16.18 Chromatin Architecture Dynamics of the IgH Locus in V（D） J Recombination，CSR，and SHM 421

16.19 Epigenetics of V（D）J Recombination，CSR，and SHM 423

16.20 B Cell Differentiation Results in Maturation of the Antibody Response and Generation of Long-lived Plasma Cells and Memory B Cells 425

16.21 The T Cell Receptor Antigen Is Related to the BCR 426

16.22 The TCR Functions in Conjunction with the MHC 427

16.23 The MHC Locus Comprises a Cohort of Genes Involved in Immune Recognition 428

PARTⅢ Transcription and Posttranscriptional Mechanisms 441

Chapter 17 Prokaryotic Transcription 442

17.1 Introduction 443

17.2 Transcription Occurs by Base Pairing in a “Bubble” of Unpaired DNA 444

17.3 The Transcription Reaction Has Three Stages 445

17.4 Bacterial RNA Polymerase Consists of Multiple Subunits 446

17.5 RNA Polymerase Holoenzyme Consists of the Core Enzyme and Sigma Factor 446

17.6 How Does RNA Polymerase Find Promoter Sequences？ 448

17.7 The Holoenzyme Goes Through Transitions in the Process of Recognizing and Escaping from Promoters 448

17.8 Sigma Factor Controls Binding to DNA by Recognizing Specific Sequences in Promoters 451

17.9 Promoter Efficiencies Can Be Increased or Decreased by Mutation 452

17.10 Multiple Regions in RNA Polymerase Directly Contact Promoter DNA 453

17.11 RNA Polymerase-Promoter and DNA-Protein Interactions Are the Same for Promoter Recognition and DNA Melting 456

17.12 Interactions Between Sigma Factor and Core RNA Polymerase Change During Promoter Escape 458

17.13 A Model for Enzyme Movement Is Suggested by the Crystal Structure 459

17.14 A Stalled RNA Polymerase Can Restart 461

17.15 Bacterial RNA Polymerase Terminates at Discrete Sites 461

17.16 How Does Rho Factor Work？ 463

17.17 Supercoiling Is an Important Feature of Transcription 465

17.18 Phage T7 RNA Polymerase Is a Useful Model System 466

17.19 Competition for Sigma Factors Can Regulate Initiation 466

17.20 Sigma Factors Can Be Organized into Cascades 468

17.21 Sporulation Is Controlled by Sigma Factors 469

17.22 Antitermination Can Be a Regulatory Event 471

Chapter 18 Eukaryotic Transcription 479

18.1 Introduction 479

18.2 Eukaryotic RNA Polymerases Consist of Many Subunits 481

18.3 RNA Polymerase Ⅰ Has a Bipartite Promoter 482

18.4 RNA Polymerase Ⅲ Uses Downstream and Upstream Promoters 483

18.5 The Start Point for RNA Polymerase Ⅱ 485

18.6 TBP Is a Universal Factor 486

18.7 The Basal Apparatus Assembles at the Promoter 488

18.8 Initiation Is Followed by Promoter Clearance and Elongation 490

18.9 Enhancers Contain Bidirectional Elements That Assist Initiation 493

18.10 Enhancers Work by Increasing the Concentration of Activators Near the Promoter 494

18.11 Gene Expression Is Associated with Demethylation 495

18.12 CpG Islands Are Regulatory Targets 496

Chapter 19 RNA Splicing and Processing 503

19.1 Introduction 503

19.2 The 5’ End of Eukaryotic mRNA Is Capped 505

19.3 Nuclear Splice Sites Are Short Sequences 506

19.4 Splice Sites Are Read in Pairs 507

19.5 Pre-mRNA Splicing Proceeds Through a Lariat 508

19.6 snRNAs Are Required for Splicing 509

19.7 Commitment of Pre-mRNA to the Splicing Pathway 510

19.8 The Spliceosome Assembly Pathway 513

19.9 An Alternative Spliceosome Uses Different snRNPs to Process the Minor Class of Introns 515

19.10 Pre-mRNA Splicing Likely Shares the Mechanism with Group Ⅱ Autocatalytic Introns 516

19.11 Splicing Is Temporally and Functionally Coupled with Multiple Steps in Gene Expression 518

19.12 Alternative Splicing Is a Rule，Rather Than an Exception，in Multicellular Eukaryotes 519

19.13 Splicing Can Be Regulated by Exonic and Intronic Splicing Enhancers and Silencers 522

19.14 trans-Splicing Reactions Use Small RNAs 524

19.15 The 3’ Ends of mRNAs Are Generated by Cleavage and Polyadenylation 526

19.16 3’ mRNA End Processing Is Critical for Termination of Transcription 528

19.17 The 3’ End Formation of Histone mRNA Requires U7 snRNA 529

19.18 tRNA Splicing Involves Cutting and Rejoining in Separate Reactions 530

19.19 The Unfolded Protein Response Is Related to tRNA Splicing 533

19.20 Production of rRNA Requires Cleavage Events and Involves Small RNAs 534

Chapter 20 mRNA Stability and Localization&Edited by Ellen Baker 543

20.1 Introduction 543

20.2 Messenger RNAs Are Unstable Molecules 544

20.3 Eukaryotic mRNAs Exist in the Form of mRNPs from Their Birth to Their Death 546

20.4 Prokaryotic mRNA Degradation Involves Multiple Enzymes 546

20.5 Most Eukaryotic mRNA Is Degraded via Two Deadenylation-Dependent Pathways 548

20.6 Other Degradation Pathways Target Specific mRNAs 550

20.7 mRNA-Specific Half-Lives Are Controlled by Sequences or Structures Within the mRNA 552

20.8 Newly Synthesized RNAs Are Checked for Defects via aNuclear Surveillance System 553

20.9 Quality Control of mRNA Translation Is Performed by Cytoplasmic Surveillance Systems 555

20.10 Translationally Silenced mRNAs Are Sequestered in a Variety of RNA Granules 557

20.11 Some Eukaryotic mRNAs Are Localized to Specific Regions of a Cell 558

Chapter 21 Catalytic RNA&Edited by Douglas J.Briant 563

21.1 Introduction 563

21.2 Group Ⅰ Introns Undertake Self-Splicing by Transesterification 564

21.3 Group Ⅰ Introns Form a Characteristic Secondary Structure 567

21.4 Ribozymes Have Various Catalytic Activities 568

21.5 Some Group Ⅰ Introns Encode Endonucleases That Sponsor Mobility 570

21.6 Group Ⅱ Introns May Encode Multifunction Proteins 571

21.7 Some Autosplicing Introns Require Maturases 572

21.8 The Catalytic Activity of RNase P Is Due to RNA 573

21.9 Viroids Have Catalytic Activity 573

21.10 RNA Editing Occurs at Individual Bases 575

21.11 RNA Editing Can Be Directed by Guide RNAs 576

21.12 Protein Splicing Is Autocatalytic 578

Chapter 22 Translation 583

22.1 Introduction 583

22.2 Translation Occurs by Initiation，Elongation，and Termination 584

22.3 Special Mechanisms Control the Accuracy of Translation 586

22.4 Initiation in Bacteria Needs 30S Subunits and Accessory Factors 587

22.5 Initiation Involves Base Pairing Between mRNA and rRNA 589

22.6 A Special Initiator tRNA Starts the Polypeptide Chain 590

22.7 Use of fMet-tRNAf Is Controlled by IF-2 and the Ribosome 591

22.8 Small Subunits Scan for Initiation Sites on Eukaryotic mRNA 592

22.9 Eukaryotes Use a Complex of Many Initiation Factors 593

22.10 Elongation Factor Tu Loads Aminoacyl-tRNA into the A Site 597

22.11 The Polypeptide Chain Is Transferred to Aminoacyl-tRNA 598

22.12 Translocation Moves the Ribosome 599

22.13 Elongation Factors Bind Alternately to the Ribosome 600

22.14 Three Codons Terminate Translation 601

22.15 Termination Codons Are Recognized by Protein Factors 602

22.16 Ribosomal RNA Is Found Throughout Both Ribosomal Subunits 604

22.17 Ribosomes Have Several Active Centers 606

22.18 16S rRNA Plays an Active Role in Translation 608

22.19 23S rRNA Has Peptidyl Transferase Activity 610

22.20 Ribosomal Structures Change When the Subunits Come Together 611

22.21 Translation Can Be Regulated 612

22.22 The Cycle of Bacterial Messenger RNA 613

Chapter 23 Using the Genetic Code 621

23.1 Introduction 621

23.2 Related Codons Represent Chemically Similar Amino Acids 622

23.3 Codon-Anticodon Recognition Involves Wobbling 623

23.4 tRNAs Are Processed from Longer Precursors 624

23.5 tRNA Contains Modified Bases 625

23.6 Modified Bases Affect Anticodon-Codon Pairing 627

23.7 The Universal Code Has Experienced Sporadic Alterations 628

23.8 Novel Amino Acids Can Be Inserted at Certain Stop Codons 630

23.9 tRNAs Are Charged with Amino Acids by Aminoacyl-tRNA Synthetases 631

23.10 Aminoacyl-tRNA Synthetases Fall into Two Classes 632

23.11 Synthetases Use Proofreading to Improve Accuracy 634

23.12 Suppressor tRNAs Have Mutated Anticodons That Read New Codons 636

23.13 Each Termination Codon Has Nonsense Suppressors 637

23.14 Suppressors May Compete with Wild-Type Reading of the Code 638

23.15 The Ribosome Influences the Accuracy of Translation 639

23.16 Frameshifting Occurs at Slippery Sequences 641

23.17 Other Recoding Events：Translational Bypassing and the tmRNA Mechanism to Free Stalled Ribosomes 642

PART Ⅳ Gene Regulation 647

Chapter 24 The Operon&Edited by Liskin Swint-Kruse 648

24.1 Introduction 649

24.2 Structural Gene Clusters Are Coordinately Controlled 651

24.3 The lac Operon Is Negative Inducible 652

24.4 The lac Repressor Is Controlled by a Small-Molecule Inducer 653

24.5 cis-Acting Constitutive Mutations Identify the Operator 655

24.6 trans-Acting Mutations Identify the Regulator Gene 655

24.7 The lac Repressor Is a Tetramer Made of Two Dimers 656

24.8 lac Repressor Binding to the Operator Is Regulated by an Allosteric Change in Conformation 658

24.9 The lac Repressor Binds to Three Operators and Interacts with RNA Polymerase 660

24.10 The Operator Competes with Low-Affinity Sites to Bind Repressor 661

24.11 The lac Operon Has a Second Layer of Control：Catabolite Repression 662

24.12 The trp Operon Is a Repressible Operon with Three Transcription Units 665

24.13 The trp Operon Is Also Controlled by Attenuation 666

24.14 Attenuation Can Be Controlled by Translation 668

24.15 Stringent Control by Stable RNA Transcription 670

24.16 r-Protein Synthesis Is Controlled by Autoregulation 671

Chapter 25 Phage Strategies 677

25.1 Introduction 677

25.2 Lytic Development Is Divided into Two Periods 679

25.3 Lytic Development Is Controlled by a Cascade 679

25.4 Two Types of Regulatory Events Control the Lytic Cascade 681

25.5 The Phage T7 and T4 Genomes Show Functional Clustering 681

25.6 Lambda Immediate Early and Delayed Early Genes Are Needed for Both Lysogeny and the Lytic Cycle 683

25.7 The Lytic Cycle Depends on Antitermination by pN 684

25.8 Lysogeny Is Maintained by the Lambda Repressor Protein 685

25.9 The Lambda Repressor and Its Operators Define the Immunity Region 686

25.10 The DNA-Binding Form of the Lambda Repressor Is a Dimer 687

25.11 The Lambda Repressor Uses a Helix-Turn-Helix Motif to Bind DNA 688

25.12 Lambda Repressor Dimers Bind Cooperatively to the Operator 689

25.13 The Lambda Repressor Maintains an Autoregulatory Circuit 690

25.14 Cooperative Interactions Increase the Sensitivity of Regulation 692

25.15 The cll and clll Genes Are Needed to Establish Lysogeny 692

25.16 A Poor Promoter Requires cll Protein 693

25.17 Lysogeny Requires Several Events 694

25.18 The Cro Repressor Is Needed for Lytic Infection 694

25.19 What Determines the Balance Between Lysogeny and the Lytic Cycle？ 697

Chapter 26 Eukaryotic Transcription Regulation 701

26.1 Introduction 702

26.2 How Is a Gene Turned On？ 703

26.3 Mechanism of Action of Activators and Repressors 704

26.4 Independent Domains Bind DNA and Activate Transcription 707

26.5 The Two-Hybrid Assay Detects Protein-Protein Interactions 707

26.6 Activators Interact with the Basal Apparatus 708

26.7 Many Types of DNA-Binding Domains Have Been Identified 711

26.8 Chromatin Remodeling Is an Active Process 712

26.9 Nucleosome Organization or Content Can Be Changed at the Promoter 715

26.10 Histone Acetylation Is Associated with Transcription Activation 716

26.11 Methylation of Histones and DNA Is Connected 719

26.12 Promoter Activation Involves Multiple Changes to Chromatin 720

26.13 Histone Phosphorylation Affects Chromatin Structure 722

26.14 Yeast GAL Genes：A Model for Activation and Repression 722

Chapter 27 Epigenetics Ⅰ&Edited by Trygve Tollefsbol 731

27.1 Introduction 731

27.2 Heterochromatin Propagates from a Nucleation Event 732

27.3 Heterochromatin Depends on Interactions with Histones 734

27.4 Polycomb and Trithorax Are Antagonistic Repressors and Activators 737

27.5 CpG Islands Are Subject to Methylation 738

27.6 Epigenetic Effects Can Be Inherited 741

27.7 Yeast Prions Show Unusual Inheritance 743

Chapter 28 Epigenetics Ⅱ&Edited by Trygve Tollefsbol 749

28.1 Introduction 749

28.2 X Chromosomes Undergo Global Changes 750

28.3 Chromosome Condensation Is Caused by Condensins 752

28.4 DNA Methylation Is Responsible for Imprinting 755

28.5 Oppositely Imprinted Genes Can Be Controlled by a Single Center 756

28.6 Prions Cause Diseases in Mammals 757

Chapter 29 Noncoding RNA 761

29.1 Introduction 761

29.2 A Riboswitch Can Alter Its Structure According to Its Environment 762

29.3 Noncoding RNAs Can Be Used to Regulate Gene Expression 763

Chapter 30 Regulatory RNA 769

30.1 Introduction 769

30.2 Bacteria Contain Regulator RNAs 770

30.3 MicroRNAs Are Widespread Regulators in Eukaryotes 772

30.4 How Does RNA Interference Work？ 775

30.5 Heterochromatin Formation Requires MicroRNAs 778

Glossary 783

Index 809

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