Lewin's GENES XII by Krebs, Jocelyn E. -- Read -- Imperial Library of Trantor

Index

Cover Page Title Page Copyright Page Dedication Brief Contents Contents Preface About the Authors PART I Genes and Chromosomes

Chapter 1 Genes Are DNA and Encode RNAs and Polypeptides

1.1 Introduction 1.2 DNA Is the Genetic Material of Bacteria and Viruses 1.3 DNA Is the Genetic Material of Eukaryotic Cells 1.4 Polynucleotide Chains Have Nitrogenous Bases Linked to a Sugar—Phosphate Backbone 1.5 Supercoiling Affects the Structure of DNA 1.6 DNA Is a Double Helix 1.7 DNA Replication Is Semiconservative 1.8 Polymerases Act on Separated DNA Strands at the Replication Fork 1.9 Genetic Information Can Be Provided by DNA or RNA 1.10 Nucleic Acids Hybridize by Base Pairing 1.11 Mutations Change the Sequence of DNA 1.12 Mutations Can Affect Single Base Pairs or Longer Sequences 1.13 The Effects of Mutations Can Be Reversed 1.14 Mutations Are Concentrated at Hotspots 1.15 Many Hotspots Result from Modified Bases 1.16 Some Hereditary Agents Are Extremely Small 1.17 Most Genes Encode Polypeptides 1.18 Mutations in the Same Gene Cannot Complement 1.19 Mutations May Cause Loss of Function or Gain of Function 1.20 A Locus Can Have Many Different Mutant Alleles 1.21 A Locus Can Have More Than One Wild-Type Allele 1.22 Recombination Occurs by Physical Exchange of DNA 1.23 The Genetic Code Is Triplet 1.24 Every Coding Sequence Has Three Possible Reading Frames 1.25 Bacterial Genes Are Colinear with Their Products 1.26 Several Processes Are Required to Express the Product of a Gene 1.27 Proteins Are trans-Acting but Sites on DNA Are cis-Acting

Chapter 2 Methods in Molecular Biology and Genetic Engineering

2.1 Introduction 2.2 Nucleases 2.3 Cloning 2.4 Cloning Vectors Can Be Specialized for Different Purposes 2.5 Nucleic Acid Detection 2.6 DNA Separation Techniques 2.7 DNA Sequencing 2.8 PCR and RT-PCR 2.9 Blotting Methods 2.10 DNA Microarrays 2.11 Chromatin Immunoprecipitation 2.12 Gene Knockouts, Transgenics, and Genome Editing

Chapter 3 The Interrupted Gene

3.1 Introduction 3.2 An Interrupted Gene Has Exons and Introns 3.3 Exon and Intron Base Compositions Differ 3.4 Organization of Interrupted Genes Can Be Conserved 3.5 Exon Sequences Under Negative Selection Are Conserved but Introns Vary 3.6 Exon Sequences Under Positive Selection Vary but Introns Are Conserved 3.7 Genes Show a Wide Distribution of Sizes Due Primarily to Intron Size and Number Variation 3.8 Some DNA Sequences Encode More Than One Polypeptide 3.9 Some Exons Correspond to Protein Functional Domains 3.10 Members of a Gene Family Have a Common Organization 3.11 There Are Many Forms of Information in DNA

Chapter 4 The Content of the Genome

4.1 Introduction 4.2 Genome Mapping Reveals That Individual Genomes Show Extensive Variation 4.3 SNPs Can Be Associated with Genetic Disorders 4.4 Eukaryotic Genomes Contain Nonrepetitive and Repetitive DNA Sequences 4.5 Eukaryotic Protein-Coding Genes Can Be Identified by the Conservation of Exons and of Genome Organization 4.6 Some Eukaryotic Organelles Have DNA 4.7 Organelle Genomes Are Circular DNAs That Encode Organelle Proteins 4.8 The Chloroplast Genome Encodes Many Proteins and RNAs 4.9 Mitochondria and Chloroplasts Evolved by Endosymbiosis

Chapter 5 Genome Sequences and Evolution

5.1 Introduction 5.2 Prokaryotic Gene Numbers Range Over an Order of Magnitude 5.3 Total Gene Number Is Known for Several Eukaryotes 5.4 How Many Different Types of Genes Are There? 5.5 The Human Genome Has Fewer Genes Than Originally Expected 5.6 How Are Genes and Other Sequences Distributed in the Genome? 5.7 The Y Chromosome Has Several Male-Specific Genes 5.8 How Many Genes Are Essential? 5.9 About 10,000 Genes Are Expressed at Widely Differing Levels in a Eukaryotic Cell 5.10 Expressed Gene Number Can Be Measured En Masse 5.11 DNA Sequences Evolve by Mutation and a Sorting Mechanism 5.12 Selection Can Be Detected by Measuring Sequence Variation 5.13 A Constant Rate of Sequence Divergence Is a Molecular Clock 5.14 The Rate of Neutral Substitution Can Be Measured from Divergence of Repeated Sequences 5.15 How Did Interrupted Genes Evolve? 5.16 Why Are Some Genomes So Large? 5.17 Morphological Complexity Evolves by Adding New Gene Functions 5.18 Gene Duplication Contributes to Genome Evolution 5.19 Globin Clusters Arise by Duplication and Divergence 5.20 Pseudogenes Have Lost Their Original Functions 5.21 Genome Duplication Has Played a Role in Plant and Vertebrate Evolution 5.22 What Is the Role of Transposable Elements in Genome Evolution 5.23 There Can Be Biases in Mutation, Gene Conversion, and Codon Usage

Chapter 6 Clusters and Repeats

6.1 Introduction 6.2 Unequal Crossing-Over Rearranges Gene Clusters 6.3 Genes for rRNA Form Tandem Repeats Including an Invariant Transcription Unit 6.4 Crossover Fixation Could Maintain Identical Repeats 6.5 Satellite DNAs Often Lie in Heterochromatin 6.6 Arthropod Satellites Have Very Short Identical Repeats 6.7 Mammalian Satellites Consist of Hierarchical Repeats 6.8 Minisatellites Are Useful for DNA Profiling

Chapter 7 Chromosomes

7.1 Introduction 7.2 Viral Genomes Are Packaged into Their Coats 7.3 The Bacterial Genome Is a Nucleoid with Dynamic Structural Properties 7.4 The Bacterial Genome Is Supercoiled and Has Four Macrodomains 7.5 Eukaryotic DNA Has Loops and Domains Attached to a Scaffold 7.6 Specific Sequences Attach DNA to an Interphase Matrix 7.7 Chromatin Is Divided into Euchromatin and Heterochromatin 7.8 Chromosomes Have Banding Patterns 7.9 Lampbrush Chromosomes Are Extended 7.10 Polytene Chromosomes Form Bands 7.11 Polytene Chromosomes Expand at Sites of Gene Expression 7.12 The Eukaryotic Chromosome Is a Segregation Device 7.13 Regional Centromeres Contain a Centromeric Histone H3 Variant and Repetitive DNA 7.14 Point Centromeres in S. cerevisiae Contain Short, Essential DNA Sequences 7.15 The S. cerevisiae Centromere Binds a Protein Complex 7.16 Telomeres Have Simple Repeating Sequences 7.17 Telomeres Seal the Chromosome Ends and Function in Meiotic Chromosome Pairing 7.18 Telomeres Are Synthesized by a Ribonucleoprotein Enzyme 7.19 Telomeres Are Essential for Survival

Chapter 8 Chromatin

8.1 Introduction 8.2 DNA Is Organized in Arrays of Nucleosomes 8.3 The Nucleosome Is the Subunit of All Chromatin 8.4 Nucleosomes Are Covalently Modified 8.5 Histone Variants Produce Alternative Nucleosomes 8.6 DNA Structure Varies on the Nucleosomal Surface 8.7 The Path of Nucleosomes in the Chromatin Fiber 8.8 Replication of Chromatin Requires Assembly of Nucleosomes 8.9 Do Nucleosomes Lie at Specific Positions? 8.10 Nucleosomes Are Displaced and Reassembled During Transcription 8.11 DNase Sensitivity Detects Changes in Chromatin Structure 8.12 An LCR Can Control a Domain 8.13 Insulators Define Transcriptionally Independent Domains

PART II DNA Replication and Recombination

Chapter 9 Replication Is Connected to the Cell Cycle

9.1 Introduction 9.2 Bacterial Replication Is Connected to the Cell Cycle 9.3 The Shape and Spatial Organization of a Bacterium Are Important During Chromosome Segregation and Cell Division 9.4 Mutations in Division or Segregation Affect Cell Shape 9.5 FtsZ Is Necessary for Septum Formation 9.6 min and noc/slm Genes Regulate the Location of the Septum 9.7 Partition Involves Separation of the Chromosomes 9.8 Chromosomal Segregation Might Require Site-Specific Recombination 9.9 The Eukaryotic Growth Factor Signal Transduction Pathway Promotes Entry to S Phase 9.10 Checkpoint Control for Entry into S Phase: p53, a Guardian of the Checkpoint 9.11 Checkpoint Control for Entry into S Phase: Rb, a Guardian of the Checkpoint

Chapter 10 The Replicon: Initiation of Replication

10.1 Introduction 10.2 An Origin Usually Initiates Bidirectional Replication 10.3 The Bacterial Genome Is (Usually) a Single Circular Replicon 10.4 Methylation of the Bacterial Origin Regulates Initiation 10.5 Initiation: Creating the Replication Forks at the Origin oriC 10.6 Multiple Mechanisms Exist to Prevent Premature Reinitiation of Replication 10.7 Archaeal Chromosomes Can Contain Multiple Replicons 10.8 Each Eukaryotic Chromosome Contains Many Replicons 10.9 Replication Origins Can Be Isolated in Yeast 10.10 Licensing Factor Controls Eukaryotic Rereplication 10.11 Licensing Factor Binds to ORC

Chapter 11 DNA Replication

11.1 Introduction 11.2 DNA Polymerases Are the Enzymes That Make DNA 11.3 DNA Polymerases Have Various Nuclease Activities 11.4 DNA Polymerases Control the Fidelity of Replication 11.5 DNA Polymerases Have a Common Structure 11.6 The Two New DNA Strands Have Different Modes of Synthesis 11.7 Replication Requires a Helicase and a Single-Stranded Binding Protein 11.8 Priming Is Required to Start DNA Synthesis 11.9 Coordinating Synthesis of the Lagging and Leading Strands 11.10 DNA Polymerase Holoenzyme Consists of Subcomplexes 11.11 The Clamp Controls Association of Core Enzyme with DNA 11.12 Okazaki Fragments Are Linked by Ligase 11.13 Separate Eukaryotic DNA Polymerases Undertake Initiation and Elongation 11.14 Lesion Bypass Requires Polymerase Replacement 11.15 Termination of Replication

Chapter 12 Extrachromosomal Replicons

12.1 Introduction 12.2 The Ends of Linear DNA Are a Problem for Replication 12.3 Terminal Proteins Enable Initiation at the Ends of Viral DNAs 12.4 Rolling Circles Produce Multimers of a Replicon 12.5 Rolling Circles Are Used to Replicate Phage Genomes 12.6 The F Plasmid Is Transferred by Conjugation Between Bacteria 12.7 Conjugation Transfers Single-Stranded DNA 12.8 Single-Copy Plasmids Have a Partitioning System 12.9 Plasmid Incompatibility Is Determined by the Replicon 12.10 The ColE1 Compatibility System Is Controlled by an RNA Regulator 12.11 How Do Mitochondria Replicate and Segregate? 12.12 D Loops Maintain Mitochondrial Origins 12.13 The Bacterial Ti Plasmid Causes Crown Gall Disease in Plants 12.14 T-DNA Carries Genes Required for Infection 12.15 Transfer of T-DNA Resembles Bacterial Conjugation

Chapter 13 Homologous and Site-Specific Recombination

13.1 Introduction 13.2 Homologous Recombination Occurs Between Synapsed Chromosomes in Meiosis 13.3 Double-Strand Breaks Initiate Recombination 13.4 Gene Conversion Accounts for Interallelic Recombination 13.5 The Synthesis-Dependent Strand-Annealing Model 13.6 The Single-Strand Annealing Mechanism Functions at Some Double-Strand Breaks 13.7 Break-Induced Replication Can Repair Double-Strand Breaks 13.8 Recombining Meiotic Chromosomes Are Connected by the Synaptonemal Complex 13.9 The Synaptonemal Complex Forms After Double-Strand Breaks 13.10 Pairing and Synaptonemal Complex Formation Are Independent 13.11 The Bacterial RecBCD System Is Stimulated by chi Sequences 13.12 Strand-Transfer Proteins Catalyze Single-Strand Assimilation 13.13 Holliday Junctions Must Be Resolved 13.14 Eukaryotic Genes Involved in Homologous Recombination

1. End Processing/Presynapsis 2. Synapsis 3. DNA Heteroduplex Extension and Branch Migration 4. Resolution

13.15 Specialized Recombination Involves Specific Sites 13.16 Site-Specific Recombination Involves Breakage and Reunion 13.17 Site-Specific Recombination Resembles Topoisomerase Activity 13.18 Lambda Recombination Occurs in an Intasome 13.19 Yeast Can Switch Silent and Active Mating-Type Loci 13.20 Unidirectional Gene Conversion Is Initiated by the Recipient MAT Locus 13.21 Antigenic Variation in Trypanosomes Uses Homologous Recombination 13.22 Recombination Pathways Adapted for Experimental Systems

Chapter 14 Repair Systems

14.1 Introduction 14.2 Repair Systems Correct Damage to DNA 14.3 Excision Repair Systems in E. coli 14.4 Eukaryotic Nucleotide Excision Repair Pathways 14.5 Base Excision Repair Systems Require Glycosylases 14.6 Error-Prone Repair and Translesion Synthesis 14.7 Controlling the Direction of Mismatch Repair 14.8 Recombination-Repair Systems in E. coli 14.9 Recombination Is an Important Mechanism to Recover from Replication Errors 14.10 Recombination-Repair of Double-Strand Breaks in Eukaryotes 14.11 Nonhomologous End Joining Also Repairs Double-Strand Breaks 14.12 DNA Repair in Eukaryotes Occurs in the Context of Chromatin 14.13 RecA Triggers the SOS System

Chapter 15 Transposable Elements and Retroviruses

15.1 Introduction 15.2 Insertion Sequences Are Simple Transposition Modules 15.3 Transposition Occurs by Both Replicative and Nonreplicative Mechanisms 15.4 Transposons Cause Rearrangement of DNA 15.5 Replicative Transposition Proceeds Through a Cointegrate 15.6 Nonreplicative Transposition Proceeds by Breakage and Reunion 15.7 Transposons Form Superfamilies and Families 15.8 The Role of Transposable Elements in Hybrid Dysgenesis 15.9 P Elements Are Activated in the Germline 15.10 The Retrovirus Life Cycle Involves Transposition-Like Events 15.11 Retroviral Genes Code for Polyproteins 15.12 Viral DNA Is Generated by Reverse Transcription 15.13 Viral DNA Integrates into the Chromosome 15.14 Retroviruses May Transduce Cellular Sequences 15.15 Retroelements Fall into Three Classes 15.16 Yeast Ty Elements Resemble Retroviruses 15.17 The Alu Family Has Many Widely Dispersed Members 15.18 LINEs Use an Endonuclease to Generate a Priming End

Chapter 16 Somatic DNA Recombination and Hypermutation in the Immune System

16.1 The Immune System: Innate and Adaptive Immunity 16.2 The Innate Response Utilizes Conserved Recognition Molecules and Signaling Pathways 16.3 Adaptive Immunity 16.4 Clonal Selection Amplifies Lymphocytes That Respond to a Given Antigen 16.5 Ig Genes Are Assembled from Discrete DNA Segments in B Lymphocytes 16.6 L Chains Are Assembled by a Single Recombination Event 16.7 H Chains Are Assembled by Two Sequential Recombination Events 16.8 Recombination Generates Extensive Diversity 16.9 V(D)J DNA Recombination Relies on RSS and Occurs by Deletion or Inversion 16.10 Allelic Exclusion Is Triggered by Productive Rearrangements 16.11 RAG1/RAG2 Catalyze Breakage and Religation of V(D)J Gene Segments 16.12 B Cell Development in the Bone Marrow: From Common Lymphoid Progenitor to Mature B Cell 16.13 Class Switch DNA Recombination 16.14 CSR Involves AID and Elements of the NHEJ Pathway 16.15 Somatic Hypermutation Generates Additional Diversity and Provides the Substrate for Higher-Affinity Submutants 16.16 SHM Is Mediated by AID, Ung, Elements of the Mismatch DNA Repair Machinery, and Translesion DNA Synthesis Polymerases 16.17 Igs Expressed in Avians Are Assembled from Pseudogenes 16.18 Chromatin Architecture Dynamics of the IgH Locus in V(D)J Recombination, CSR, and SHM 16.19 Epigenetics of V(D)J Recombination, CSR, and SHM 16.20 B Cell Differentiation Results in Maturation of the Antibody Response and Generation of Long-lived Plasma Cells and Memory B Cells 16.21 The T Cell Receptor Antigen Is Related to the BCR 16.22 The TCR Functions in Conjunction with the MHC 16.23 The MHC Locus Comprises a Cohort of Genes Involved in Immune Recognition

PART III Transcription and Posttranscriptional Mechanisms

Chapter 17 Prokaryotic Transcription

17.1 Introduction 17.2 Transcription Occurs by Base Pairing in a "Bubble" of Unpaired DNA 17.3 The Transcription Reaction Has Three Stages 17.4 Bacterial RNA Polymerase Consists of Multiple Subunits 17.5 RNA Polymerase Holoenzyme Consists of the Core Enzyme and Sigma Factor 17.6 How Does RNA Polymerase Find Promoter Sequences? 17.7 The Holoenzyme Goes Through Transitions in the Process of Recognizing and Escaping from Promoters 17.8 Sigma Factor Controls Binding to DNA by Recognizing Specific Sequences in Promoters 17.9 Promoter Efficiencies Can Be Increased or Decreased by Mutation 17.10 Multiple Regions in RNA Polymerase Directly Contact Promoter DNA 17.11 RNA Polymerase—Promoter and DNA—Protein Interactions Are the Same for Promoter Recognition and DNA Melting 17.12 Interactions Between Sigma Factor and Core RNA Polymerase Change During Promoter Escape 17.13 A Model for Enzyme Movement Is Suggested by the Crystal Structure 17.14 A Stalled RNA Polymerase Can Restart 17.15 Bacterial RNA Polymerase Terminates at Discrete Sites 17.16 How Does Rho Factor Work? 17.17 Supercoiling Is an Important Feature of Transcription 17.18 Phage T7 RNA Polymerase Is a Useful Model System 17.19 Competition for Sigma Factors Can Regulate Initiation 17.20 Sigma Factors Can Be Organized into Cascades 17.21 Sporulation Is Controlled by Sigma Factors 17.22 Antitermination Can Be a Regulatory Event

Chapter 18 Eukaryotic Transcription

18.1 Introduction 18.2 Eukaryotic RNA Polymerases Consist of Many Subunits 18.3 RNA Polymerase I Has a Bipartite Promoter 18.4 RNA Polymerase III Uses Downstream and Upstream Promoters 18.5 The Start Point for RNA Polymerase II 18.6 TBP Is a Universal Factor 18.7 The Basal Apparatus Assembles at the Promoter 18.8 Initiation Is Followed by Promoter Clearance and Elongation 18.9 Enhancers Contain Bidirectional Elements That Assist Initiation 18.10 Enhancers Work by Increasing the Concentration of Activators Near the Promoter 18.11 Gene Expression Is Associated with Demethylation 18.12 CpG Islands Are Regulatory Targets

Chapter 19 RNA Splicing and Processing

19.1 Introduction 19.2 The 5ʹ End of Eukaryotic mRNA Is Capped 19.3 Nuclear Splice Sites Are Short Sequences 19.4 Splice Sites Are Read in Pairs 19.5 Pre-mRNA Splicing Proceeds Through a Lariat 19.6 snRNAs Are Required for Splicing 19.7 Commitment of Pre-mRNA to the Splicing Pathway 19.8 The Spliceosome Assembly Pathway 19.9 An Alternative Spliceosome Uses Different snRNPs to Process the Minor Class of Introns 19.10 Pre-mRNA Splicing Likely Shares the Mechanism with Group II Autocatalytic Introns 19.11 Splicing Is Temporally and Functionally Coupled with Multiple Steps in Gene Expression 19.12 Alternative Splicing Is a Rule, Rather Than an Exception, in Multicellular Eukaryotes 19.13 Splicing Can Be Regulated by Exonic and Intronic Splicing Enhancers and Silencers 19.14 trans-Splicing Reactions Use Small RNAs 19.15 The 3ʹ Ends of mRNAs Are Generated by Cleavage and Polyadenylation 19.16 3ʹ mRNA End Processing Is Critical for Termination of Transcription 19.17 The 3ʹ End Formation of Histone mRNA Requires U7 snRNA 19.18 tRNA Splicing Involves Cutting and Rejoining in Separate Reactions 19.19 The Unfolded Protein Response Is Related to tRNA Splicing 19.20 Production of rRNA Requires Cleavage Events and Involves Small RNAs

Chapter 20 mRNA Stability and Localization

20.1 Introduction 20.2 Messenger RNAs Are Unstable Molecules 20.3 Eukaryotic mRNAs Exist in the Form of mRNPs from Their Birth to Their Death 20.4 Prokaryotic mRNA Degradation Involves Multiple Enzymes 20.5 Most Eukaryotic mRNA Is Degraded via Two Deadenylation-Dependent Pathways 20.6 Other Degradation Pathways Target Specific mRNAs 20.7 mRNA-Specific Half-Lives Are Controlled by Sequences or Structures Within the mRNA 20.8 Newly Synthesized RNAs Are Checked for Defects via a Nuclear Surveillance System 20.9 Quality Control of mRNA Translation Is Performed by Cytoplasmic Surveillance Systems 20.10 Translationally Silenced mRNAs Are Sequestered in a Variety of RNA Granules 20.11 Some Eukaryotic mRNAs Are Localized to Specific Regions of a Cell

Chapter 21 Catalytic RNA

21.1 Introduction 21.2 Group I Introns Undertake Self-Splicing by Transesterification 21.3 Group I Introns Form a Characteristic Secondary Structure 21.4 Ribozymes Have Various Catalytic Activities 21.5 Some Group I Introns Encode Endonucleases That Sponsor Mobility 21.6 Group II Introns May Encode Multifunction Proteins 21.7 Some Autosplicing Introns Require Maturases 21.8 The Catalytic Activity of RNase P Is Due to RNA 21.9 Viroids Have Catalytic Activity 21.10 RNA Editing Occurs at Individual Bases 21.11 RNA Editing Can Be Directed by Guide RNAs 21.12 Protein Splicing Is Autocatalytic

Chapter 22 Translation

22.1 Introduction 22.2 Translation Occurs by Initiation, Elongation, and Termination 22.3 Special Mechanisms Control the Accuracy of Translation 22.4 Initiation in Bacteria Needs 30S Subunits and Accessory Factors 22.5 Initiation Involves Base Pairing Between mRNA and rRNA 22.6 A Special Initiator tRNA Starts the Polypeptide Chain 22.7 Use of fMet-tRNAf Is Controlled by IF-2 and the Ribosome 22.8 Small Subunits Scan for Initiation Sites on Eukaryotic mRNA 22.9 Eukaryotes Use a Complex of Many Initiation Factors 22.10 Elongation Factor Tu Loads Aminoacyl-tRNA into the A Site 22.11 The Polypeptide Chain Is Transferred to Aminoacyl-tRNA 22.12 Translocation Moves the Ribosome 22.13 Elongation Factors Bind Alternately to the Ribosome 22.14 Three Codons Terminate Translation 22.15 Termination Codons Are Recognized by Protein Factors 22.16 Ribosomal RNA Is Found Throughout Both Ribosomal Subunits 22.17 Ribosomes Have Several Active Centers 22.18 16S rRNA Plays an Active Role in Translation 22.19 23S rRNA Has Peptidyl Transferase Activity 22.20 Ribosomal Structures Change When the Subunits Come Together 22.21 Translation Can Be Regulated 22.22 The Cycle of Bacterial Messenger RNA

Chapter 23 Using the Genetic Code

23.1 Introduction 23.2 Related Codons Represent Chemically Similar Amino Acids 23.3 Codon—Anticodon Recognition Involves Wobbling 23.4 tRNAs Are Processed from Longer Precursors 23.5 tRNA Contains Modified Bases 23.6 Modified Bases Affect Anticodon—Codon Pairing 23.7 The Universal Code Has Experienced Sporadic Alterations 23.8 Novel Amino Acids Can Be Inserted at Certain Stop Codons 23.9 tRNAs Are Charged with Amino Acids by Aminoacyl-tRNA Synthetases 23.10 Aminoacyl-tRNA Synthetases Fall into Two Classes 23.11 Synthetases Use Proofreading to Improve Accuracy 23.12 Suppressor tRNAs Have Mutated Anticodons That Read New Codons 23.13 Each Termination Codon Has Nonsense Suppressors 23.14 Suppressors May Compete with Wild-Type Reading of the Code 23.15 The Ribosome Influences the Accuracy of Translation 23.16 Frameshifting Occurs at Slippery Sequences 23.17 Other Recoding Events: Translational Bypassing and the tmRNA Mechanism to Free Stalled Ribosomes

PART IV Gene Regulation

Chapter 24 The Operon

24.1 Introduction 24.2 Structural Gene Clusters Are Coordinately Controlled 24.3 The lac Operon Is Negative Inducible 24.4 The lac Repressor Is Controlled by a Small-Molecule Inducer 24.5 cis-Acting Constitutive Mutations Identify the Operator 24.6 trans-Acting Mutations Identify the Regulator Gene 24.7 The lac Repressor Is a Tetramer Made of Two Dimers 24.8 lac Repressor Binding to the Operator Is Regulated by an Allosteric Change in Conformation 24.9 The lac Repressor Binds to Three Operators and Interacts with RNA Polymerase 24.10 The Operator Competes with Low-Affinity Sites to Bind Repressor 24.11 The lac Operon Has a Second Layer of Control: Catabolite Repression 24.12 The trp Operon Is a Repressible Operon with Three Transcription Units 24.13 The trp Operon Is Also Controlled by Attenuation 24.14 Attenuation Can Be Controlled by Translation 24.15 Stringent Control by Stable RNA Transcription 24.16 r-Protein Synthesis Is Controlled by Autoregulation

Chapter 25 Phage Strategies

25.1 Introduction 25.2 Lytic Development Is Divided into Two Periods 25.3 Lytic Development Is Controlled by a Cascade 25.4 Two Types of Regulatory Events Control the Lytic Cascade 25.5 The Phage T7 and T4 Genomes Show Functional Clustering 25.6 Lambda Immediate Early and Delayed Early Genes Are Needed for Both Lysogeny and the Lytic Cycle 25.7 The Lytic Cycle Depends on Antitermination by pN 25.8 Lysogeny Is Maintained by the Lambda Repressor Protein 25.9 The Lambda Repressor and Its Operators Define the Immunity Region 25.10 The DNA-Binding Form of the Lambda Repressor Is a Dimer 25.11 The Lambda Repressor Uses a Helix-Turn-Helix Motif to Bind DNA 25.12 Lambda Repressor Dimers Bind Cooperatively to the Operator 25.13 The Lambda Repressor Maintains an Autoregulatory Circuit 25.14 Cooperative Interactions Increase the Sensitivity of Regulation 25.15 The cII and cIII Genes Are Needed to Establish Lysogeny 25.16 A Poor Promoter Requires cII Protein 25.17 Lysogeny Requires Several Events 25.18 The Cro Repressor Is Needed for Lytic Infection 25.19 What Determines the Balance Between Lysogeny and the Lytic Cycle?

Chapter 26 Eukaryotic Transcription Regulation

26.1 Introduction 26.2 How Is a Gene Turned On? 26.3 Mechanism of Action of Activators and Repressors 26.4 Independent Domains Bind DNA and Activate Transcription 26.5 The Two-Hybrid Assay Detects Protein—Protein Interactions 26.6 Activators Interact with the Basal Apparatus 26.7 Many Types of DNA-Binding Domains Have Been Identified 26.8 Chromatin Remodeling Is an Active Process 26.9 Nucleosome Organization or Content Can Be Changed at the Promoter 26.10 Histone Acetylation Is Associated with Transcription Activation 26.11 Methylation of Histones and DNA Is Connected 26.12 Promoter Activation Involves Multiple Changes to Chromatin 26.13 Histone Phosphorylation Affects Chromatin Structure 26.14 Yeast GAL Genes: A Model for Activation and Repression

Chapter 27 Epigenetics I

27.1 Introduction 27.2 Heterochromatin Propagates from a Nucleation Event 27.3 Heterochromatin Depends on Interactions with Histones 27.4 Polycomb and Trithorax Are Antagonistic Repressors and Activators 27.5 CpG Islands Are Subject to Methylation 27.6 Epigenetic Effects Can Be Inherited 27.7 Yeast Prions Show Unusual Inheritance

Chapter 28 Epigenetics II

28.1 Introduction 28.2 X Chromosomes Undergo Global Changes 28.3 Chromosome Condensation Is Caused by Condensins 28.4 DNA Methylation Is Responsible for Imprinting 28.5 Oppositely Imprinted Genes Can Be Controlled by a Single Center 28.6 Prions Cause Diseases in Mammals

Chapter 29 Noncoding RNA

29.1 Introduction 29.2 A Riboswitch Can Alter Its Structure According to Its Environment 29.3 Noncoding RNAs Can Be Used to Regulate Gene Expression

Chapter 30 Regulatory RNA

30.1 Introduction 30.2 Bacteria Contain Regulator RNAs 30.3 MicroRNAs Are Widespread Regulators in Eukaryotes 30.4 How Does RNA Interference Work? 30.5 Heterochromatin Formation Requires MicroRNAs

Glossary Index

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