Essential GENES

Benjamin Lewin

Part 1 Genes

19 Homologous andSite-Specific Recombination 33 4

1 DNA Is the Hereditary

20 Repair Systems Handl eMaterial

1

Damage to DNA

3562 Genes Code for Proteins

23

21 Transposons

3723 Genes May Be Interrupted 38

22 Retroviruses and4 The Content of the Genome 54

Retroposons

3925 Genome Sequences

23 Recombination inand Gene Numbers

72

the Immune System

4096 Clusters and Repeats

90

Part 5 Eukaryotic Gen ePart 2 Proteins Expression7 Messenger RNA

1138 Protein Synthesis

134

24 Promoters and Enhancers 42 99 Using the Genetic Code

162

25 Regulating Eukaryotic10 Protein Localization

Transcription

449Requires Special Signals

181

26 RNA Splicing andProcessing

468

Part 3 Gene Expression

27 Catalytic RNA

490

11 Transcription

194

Part 6 The Nucleu s12 The Operon

22213 Regulatory RNA

243

28 Chromosomes

50714 Phage Strategies

258

29 Nucleosomes

52630 Chromatin Structure Is

a Focus for Regulation

550Part 4 DNA Replication and

31 Epigenetic Effects AreRecombination

Inherited

56532 Genetic Engineering

58115 The Replicon

28016 Extrachromosomal

Glossary

G-1Replicons

29017 Bacterial Replication I s

Connected to the Cell Cycle 30 318 DNA Replication

317

Index

1-1

Part 1 GenesDNA Is the Hereditary Materia l

1 .1

Introduction

11 .2

DNA Is the Genetic Material of Bacteria

21 .3

DNA Is the Genetic Material of Viruses

31 .4

DNA Is the Genetic Material of Animal Cells

41 .5

Polynucleotide Chains Have Nitrogenous Bases Linked t oa Sugar-Phosphate Backbone

41 .6

DNA Is a Double Helix

51 .7

Supercoiling Affects the Structure of DNA

81 .8 The Structure of DNA Allows Replication and Transcription

91 .9

DNA Replication Is Semiconservative

1 11 .10 DNA Strands Separate at the Replication Fork

1 21 .11 Genetic Information Can Be Provided by DNA or RNA

1 21 .12 Nucleic Acids Hybridize by Base Pairing

1 41 .13 Mutations Change the Sequence of DNA

1 51 .14 Mutations May Affect Single Base Pairs or Longer Sequences

1 61 .15 The Effects of Mutations Can Be Reversed

1 81 .16 Mutations Are Concentrated at Hotspots

1 91 .17 Many Hotspots Result from Modified Bases

201 .18 Genomes Vary Greatly in Size

201 .19 Summary

22

Genes Code for Proteins

2

2.1 Introduction

232.2 A Gene Codes for a Single Polypeptide

242.3 Mutations in the Same Gene Cannot Complement

252.4 Mutations May Cause Loss-of-Function or Gain-of-Function

262.5 A Locus May Have Many Different Mutant Alleles

272.6 A Locus May Have More Than One Wild-Type Allele

282.7 Recombination Occurs by Physical Exchange of DNA

292.8 The Probability of Recombination Depends on Distance Apart

302.9 The Genetic Code is Triplet

3 12.10 Every Sequence Has Three Possible Reading Frames

332.11 Several Processes Are Required to Express the Protein Product of a Gene

342.12 Proteins Are trans-Acting but Sites on DNA Are cis-Acting

352.13 Summary

37

Genes May Be Interrupted3.1

Introduction

383.2 Interrupted Genes Were First Detected by Comparing mRNA and DNA

393.3 Interrupted Genes Are Much Longer than the Corresponding mRNAs

413.4 Organization of Interrupted Genes Is Often Conserved

433.5 Exon Sequences Are Conserved but Introns Vary

443.6 Genes Show a Wide Distribution of Lengths

45

3.7 Some DNA Sequences Code for More than One Protein

463 .8

How Did Interrupted Genes Evolve?

483.9 Some Exons Can Be Equated with Protein Functions

503.10 The Members of a Gene Family Have a Common Organization

5 13.11 Pseudogenes Are Dead Ends of Evolution

523.12 Summary

53

The Content of the Genome

4

4.1 Introduction

544.2 Genomes Can Be Mapped by Linkage, Restriction Cleavage, or DNA Sequence 5 54.3

Individual Genomes Show Extensive Variation

564.4 RFLPs and SNPs Can Be Used for Genetic Mapping

584.5 Why Are Genomes So Large?

604.6

Eukaryotic Genomes Contain Both Nonrepetitive and Repetitive DNA Sequences 6 14.7 Genes Can Be Isolated by the Conservation of Exons

624.8

Genes Involved in Diseases Can Be Identified by Comparing Patien tDNA with Normal DNA

644.9 The Conservation of Genome Organization Helps to Identify Genes

654.10 Organelles Have DNA

674.11 Mitochondrial Genomes Are Circular DNAs that Code for Organelle Proteins

684.12 The Chloroplast Genome Codes for Many Proteins and RNAs

704.13 Organelles Evolved by Endosymbiosis

704.14 Summary

7 1

Genome Sequences and Gene Numbers

5

5.1 Introduction

725.2 Bacterial Gene Numbers Range Over an Order of Magnitude

735.3 Total Gene Number Is Known for Several Eukaryotes

755.4 The Human Genome Has Fewer Genes than Expected

765.5 How Are Genes and Other Sequences Distributed in the Genome?

785.6 The Y Chromosome Has Several Male-Specific Genes

795.7 How Many Different Types of Genes Are There?

8 15.8 More Complex Species Evolve by Adding New Gene Functions

835.9 How Many Genes Are Essential?

845.10 About 10,000 Genes Are Expressed at Widely Different Level s

in a Eukaryotic Tissue

865.11 Expressed Gene Number Can Be Measured en masse

885 .12 Summary

89

Clusters and Repeats

6

6.1 Introduction

906.2

Gene Duplication Is a Major Force in Evolution

926.3

Globin Clusters Are Formed by Duplication and Divergence

92

6.4

Sequence Divergence Is the Basis for the Evolutionary Clock

946.5 The Rate of Neutral Substitution Can Be Measured from Divergenc e

of Repeated Sequences

976.6 Unequal Crossing-Over Rearranges Gene Clusters

98

6.7

Genes for rRNA Form Tandem Repeats Including an Invariant Transcription Unit 10 06.8

Crossover Fixation Could Maintain Identical Repeats

1026.9

Satellite DNAs Often Lie in Heterochromatin

104

6.10 Arthropod Satellites Have Very Short Identical Repeats

106

6.11 Mammalian Satellites Consist of Hierarchical Repeats

1076.12 Minisatellites Are Useful for Genetic Mapping

1096.13 Summary

112

Part 2 ProteinsMessenger RNA

4,;a

7 .1

Introduction

11 37 .2

mRNA Is Produced by Transcription and Is Translated

11 47.3 Transfer RNA Forms a Cloverleaf

11 57.4 The Acceptor Stem and Anticodon Are at Ends of the Tertiary Structure

11 77.5

Messenger RNA Is Translated by Ribosomes

11 87.6 Many Ribosomes Bind to One mRNA

11 97.7 The Life Cycle of Bacterial Messenger RNA

12 17.8

Eukaryotic mRNA Is Modified During or After Its Transcription

1237.9 The 5' End of Eukaryotic mRNA Is Capped

1247.10 The Eukaryotic mRNA 3' Terminus Is Polyadenylated

1257 .11 Bacterial mRNA Degradation Involves Multiple Enzymes

1267 .12 Two Pathways Degrade Eukaryotic mRNA

1277 .13 Nonsense Mutations Trigger a Eukaryotic Surveillance System

1297.14 Eukaryotic RNAs Are Transported

1307.15 mRNAs Can Be Localized Within a Cell

13 17.16 Summary

133

Protein Synthesis

8

8.1 Introduction

1348.2

Protein Synthesis Occurs by Initiation, Elongation, and Termination

1368.3 Special Mechanisms Control the Accuracy of Protein Synthesis

1388.4

Initiation in Bacteria Needs 30S Subunits and Accessory Factors

1398.5

A Special Initiator tRNA Starts the Polypeptide Chain

14 18 .6

mRNA Binds a 30S Subunit to Create the Binding Sit efor a Complex of IF-2 and fMet-tRNAf

1428.7

Small Eukaryotic Subunits Scan for Initiation Sites on mRNA

1448.8 Elongation Factor Tu Loads Aminoacyl-tRNA into the A Site

1468.9 The Polypeptide Chain Is Transferred to Aminoacyl-tRNA

1478.10 Translocation Moves the Ribosome

1488.11 Elongation Factors Bind Alternately to the Ribosome

1508.12 Uncharged tRNA Causes the Ribosome to Trigger the Stringent Response

1508.13 Three Codons Terminate Protein Synthesis and Are Recognize d

by Protein Factors

1538.14 Ribosomal RNA Pervades Both Ribosomal Subunits

1558.15 Ribosomes Have Several Active Centers

1568.16 Both rRNAs Play Active Roles in Protein Synthesis

1588.17 Summary

160

Using the Genetic Code9.1

Introduction

1629.2 Related Codons Represent Related Amino Acids

1639.3

Codon-Anticodon Recognition Involves Wobbling

1649.4 tRNA Contains Modified Bases

1659.5 Modified Bases Affect Anticodon-Codon Pairing

1679 .6 There Are Sporadic Alterations of the Universal Code

1689 .7 Novel Amino Acids Can Be Inserted at Certain Stop Codons

1699.8 tRNAs Are Charged with Amino Acids by Synthetases

1709.9 Aminoacyl-tRNA Synthetases Fall into Two Groups

1719.10 Synthetases Use Proofreading to Improve Accuracy

1729.11 Suppressor tRNAs Have Mutated Anticodons that Read New Codons

174

9.12 Recoding Changes Codon Meanings

1769.13 Frameshifting Occurs at Slippery Sequences

1779.14 Bypassing Involves Ribosome Movement

1799.15 Summary

180

Protein Localization Requires Special Signals

10 10.1 Introduction

18 110.2

Protein Translocation May Be Post-Translational or Co-Translational

18210.3 The Signal Sequence Interacts with the SRP

18410.4 The SRP Interacts with the SRP Receptor

18610.5 The Translocon Forms a Pore

18810.6

Post-Translational Membrane Insertion Depends on Leader Sequences

18910.7

Bacteria Use Both Co-Translational and Post-Translational Translocation

19 110.8 Summary

193

Part 3 Gene ExpressionTranscription

11 .1

Introduction

19411 .2 Transcription Occurs by Base Pairing in a "Bubble" of Unpaired DNA

19611 .3

The Transcription Reaction Has Three Stages

19611 .4 A Model for Enzyme Movement Is Suggested by the Crystal Structure

19811 .5 RNA Polymerase Consists of the Core Enzyme and Sigma Factor

20011 .6 How Does RNA Polymerase Find Promoter Sequences?

20211 .7 Sigma Factor Controls Binding to DNA

20311 .8 Promoter Recognition Depends on Consensus Sequences

20511 .9

Promoter Efficiencies Can Be Increased or Decreased by Mutation

20711 .10 Supercoiling Is an Important Feature of Transcription

20811 .11 Substitution of Sigma Factors May Control Initiation

20911 .12 Sigma Factors Directly Contact DNA

21 211 .13 There Are Two Types of Terminators in E. coli

21 311 .14 Intrinsic Termination Requires a Hairpin and U-Rich Region

21 411 .15 How Does Rho Factor Work?

21 5

11 .16 Antitermination Is a Regulatory Event

21 6

11 .17 Summary

220

The Operon

1 2

12 .1 Introduction

22 2

12.2

Structural Gene Clusters Are Coordinately Controlled

224

12.3 The lac Genes Are Controlled by a Repressor

225

12.4 The lac Operon Can Be Induced

22612.5

Repressor Is Controlled by a Small Molecule Inducer

227

12.6

cis-Acting Constitutive Mutations Identify the Operator

228

12.7

trans-Acting Mutations Identify the Regulator Gene

229

12.8 Repressor Is a Tetramer Made of Two Dimers

23 112.9

Repressor Binding to the Operator Is Regulatedby an Allosteric Change in Conformation

232

12.10 Repressor Binds to Three Operators and Interacts with RNA Polymerase

234

12.11 The Operator Competes with Low-Affinity Sites to Bind Repressor

235

12.12 Repression Can Occur at Multiple Loci

237

12.13 Operons May Be Repressed or Induced

238

12.14 Cyclic AMP Is an Inducer That Activates CRP to Act at Many Operons

239

12.15 Translation Can Be Regulated

240

12.16 Summary

241

Regulatory RNAe, !

13.1

Introduction

24313.2

Alternative Secondary Structures Can Affect Translation or Transcription

244_

13.3

Termination of 8. subtilis Tip Genes Is Controlled by Tryptophan and by tRNA T̀ '

245'1"

13.4

The E. coil tryptophan Operon Is Controlled by Attenuation

24613.5

Attenuation Can Be Controlled by Translation

24713.6 Antisense RNA Can Be Used to Inactivate Gene Expression

25013.7

Small RNA Molecules Can Regulate Translation

25 113.8

Bacteria Contain Regulator RNAs

25213.9 MicroRNAs Are Regulators in Many Eukaryotes

25413.10 RNA Interference Is Related to Gene Silencing

25513.11 Summary

257

Phage Strategies

14 14.1 Introduction

25814.2

Lytic Development Is Divided into Two Periods

25914.3 Lytic Development Is Controlled by a Cascade

26 114.4 Two Types of Regulatory Event Control the Lytic Cascade

26214.5 Lambda Uses Immediate Early and Delayed Early Gene s

for Both Lysogeny and the Lytic Cycle

26414.6

The Lytic Cycle Depends on Antitermination

26414.7

Lysogeny Is Maintained by Repressor Protein

26614.8 The Repressor and Its Operators Define the Immunity Region

26714.9 The DNA-Binding Form of Repressor Is a Dimer

26814.10 Repressor Uses a Helix-Turn-Helix Motif to Bind DNA

26914.11 Repressor Dimers Bind Cooperatively to the Operator

27014.12 Repressor Maintains an Autogenous Circuit

27214.13 Cooperative Interactions Increase the Sensitivity of Regulation

27214.14 The cl/ and c/Il Genes Are Needed to Establish Lysogeny

27314.15 Lysogeny Requires Several Events

27414.16 The Cro Repressor Is Needed for Lytic Infection

27614.17 What Determines the Balance Between Lysogeny and the Lytic Cycle?

27714.18 Summary

278

Part 4 DNA Replication and RecombinationThe Replicon

1 5

15 .1 Introduction

28015.2

An Origin Usually Initiates Bidirectional Replication

28 115.3 The Bacterial Genome Is a Single Circular Replicon

28215.4

Methylation of the Bacterial Origin Regulates Initiation

28415.5 Each Eukaryotic Chromosome Contains Many Replicons

28515.6

Replication Origins Bind the ORC

28615.7 Licensing Factor Controls Rereplication and Consists of MCM Proteins

28715.8 Summary

289

Extrachromosomal Replicons

16 16.1 Introduction

29016.2 The Ends of Linear DNA Are a Problem for Replication

29 116.3 Terminal Proteins Enable Initiation at the Ends of Viral DNAs

29216.4

Rolling Circles Produce Multimers of a Replicon

29316.5 Rolling Circles Are Used to Replicate Phage Genomes

29516.6 The F Plasmid Is Transferred by Conjugation Between Bacteria

296

16.7

Conjugation Transfers Single-Stranded DNA

29716.8

The Ti Bacterial Plasmid Transfers Genes into Plant Cells

29816.9 Transfer of T -DNA Resembles Bacterial Conjugation

29916.10 Summary

302

Bacterial Replication Is Connected to the Cell Cycle

1 7

17.1 Introduction

30317.2 Bacteria Can Have Multiforked Chromosomes

30417.3 The Septum Divides a Bacterium into Progen y

Each Containing a Chromosome

30517.4

Mutations in Division or Segregation Affect Cell Shape

30617.5 FtsZ Is Necessary for Septum Formation

30717.6 min Genes Regulate the Location of the Septum

30817.7

Chromosomal Segregation May Require Site-Specific Recombination

30917.8

Partitioning Separates the Chromosomes

31017.9

Single-Copy Plasmids Have a Partitioning System

31217.10 Plasmid Incompatibility Is Determined by the Replicon

31417.11 How Do Mitochondria Replicate and Segregate?

31517.12 Summary

316

DNA Replication

8

18.1 Introduction

31 718.2 DNA Polymerases Are the Enzymes that Make DNA

31818.3

DNA Polymerases Control the Fidelity of Replication

31 918.4 DNA Polymerases Have a Common Structure

32018.5 The Two New DNA Strands Have Different Modes of Synthesis

32 118.6

Replication Requires a Helicase and Single-Strand Binding Protein

32218.7

Priming Is Required to Start DNA Synthesis

32318.8 DNA Polymerase Holoenzyme Consists of Subcomplexes

32418.9 The Clamp Controls Association of Core Enzyme with DNA

32518.10 Coordinating the Synthesis of the Lagging and Leading Strands

32618.11 Okazaki Fragments Are Linked by Ligase

32818.12 Separate Eukaryotic DNA Polymerases Undertake Initiation and Elongation

32918.13 Creating the Replication Forks at an Origin

33018.14 The Primosome Is Needed to Restart Replication

33 118.15 Summary

333

Homologous and Site-Specific Recombination

1 9

19.1 Introduction

33419.2 Breakage and Reunion Involves Heteroduplex DNA

33519.3

Double-Strand Breaks Initiate Recombination

33819.4 Recombining Chromosomes Are Connected by the Synaptonemal Complex 33 9

19.5 The Synaptonemal Complex Forms After Double-Strand Breaks

34019.6 RecBCD Generates Free Ends for Recombination

342

19.7

Strand-Transfer Proteins Catalyze Single-Strand Assimilation

343

19.8 The Ruv System Resolves Holliday Junctions

344

19.9 Topoisomerases Relax or Introduce Supercoils in DNA

34519.10 Topoisomerases Break and Reseal Strands

346

19.11 Site-Specific Recombination Resembles Topoisomerase Activity

347

19.12 Specialized Recombination in Phage Lambda Involves Specific Sites

34919.13 Yeast Mating Type Is Changed by Recombination

351

19.14 Unidirectional Transposition Is Initiated by the Recipient MATLocus

353

19.15 Summary

354

Repair Systems Handle Damage to DNA20.1

Introduction

35620.2

Mutational Damage Falls into Two General Types

35820.3

Excision Repair Systems in E cols

360`

20 .4

Base Flipping Is Used by Methylases and Glycosylases

36120.5

Error-Prone Repair and Mutator Phenotypes

36220.6

Controlling the Direction of Mismatch Repair

36320.7

Recombination-Repair Systems in E. coil

36520.8

Recombination Is Important for Correcting Replication Errors

36620.9 Eukaryotic Cells Have Conserved Repair Systems

36720.10 A Common System Repairs Double-Strand Breaks

36820.11 Defects in Repair Systems Cause Mutations to Accumulate in Tumors

37020.12 Summary

37 1

Transposons2

21 .1 Introduction

37221 .2

Insertion Sequences Are Simple Transposition Modules

37321 .3 Composite Transposons Have IS Modules

37421 .4 Transposition Occurs by Both Replicative and Nonreplicative Mechanisms

37521 .5 Transposons Cause Rearrangement of DNA

37721 .6 Common Intermediates for Transposition

37821 .7

Replicative Transposition Proceeds Through a Cointegrate

38021 .8

Nonreplicative Transposition Proceeds by Breakage and Reunion

38 121 .9 TnA Transposition Requires Transposase and Resolvase

38221 .10 Controlling Elements in Maize Cause Breakage and Rearrangements

38421 .11 Controlling Elements Form Families of Transposons

38621 .12 Transposition of P Elements Causes Hybrid Dysgenesis

38821 .13 Summary

39 1

Retroviruses and Retroposons

2 2

22.1 Introduction

39222.2

The Retrovirus Life Cycle Involves Transposition-like Events

39322.3

Retroviral Genes Code for Polyproteins

39422.4 Viral DNA Is Generated by Reverse Transcription

39522.5 Viral DNA Integrates Into the Chromosome

39822.6 Retroviruses May Transduce Cellular Sequences

39922.7 Yeast Ty Elements Resemble Retroviruses

40022.8 Many Transposable Elements Reside in D. melanogaster

40122.9 Retroposons Fall into Three Classes

40222.10 The Alu Family Has Many Widely Dispersed Members

40422.11 Processed Pseudogenes Originated as Substrates for Transposition

40522.12 LINES Use an Endonuclease to Generate a Priming End

40622.13 Summary

408

Recombination in the Immune System

2323.1 Introduction

40923.2 Immunoglobulin Genes Are Assembled from Their Parts in Lymphocytes

41 123 .3 Light Chains Are Assembled by a Single Recombination

41 323.4 Heavy Chains Are Assembled by Two Recombinations

41 523.5 Recombination Generates Extensive Diversity

41623.6 Immune Recombination Uses Two Types of Consensus Sequence

41723.7

Recombination Generates Deletions or Inversions

41823.8 The RAG Proteins Catalyze Breakage and Reunion

419

23.9 Class Switching Is Caused by a Novel Type of DNA Recombination

42223.10 Somatic Mutation Is Induced by Cytidine Deaminase and Uracil Glycosylase 42423.11 Avian Immunoglobulins Are Assembled from Pseudogenes

42523.12 T-Cell Receptors Are Related to Immunoglobulins

42723.13 Summary

428

Part 5 Eukaryotic Gene Expressio nPromoters and Enhancers

2424.1 Introduction

42924.2 Eukaryotic RNA Polymerases Consist of Many Subunits

43 124.3 RNA Polymerase I Has a Bipartite Promoter

43224.4 RNA Polymerase III Uses Both Downstream and Upstream Promoters

43324.5 The Startpoint for RNA Polymerase II

43524.6 TBP Is a Component of TF 11 D and Binds the TATA Box

43624.7 The Basal Apparatus Assembles at the Promoter

43824.8

Initiation Is Followed by Promoter Clearance

43924.9 Short Sequence Elements Bind Activators

44024.10 Enhancers Contain Bidirectional Elements that Assist Initiation

44224.11 Enhancers Contain the Same Elements that Are Found at Promoters

44324.12 Enhancers Work by Increasing the Concentratio n

of Activators Near the Promoter

44524.13 CpG Islands Are Regulatory Targets

44624.14 Summary

448

Regulating Eukaryotic Transcription

2525.1 Introduction

44925.2 There Are Several Types of Transcription Factors

45025.3 Independent Domains Bind DNA and Activate Transcription

45125.4 Activators Interact with the Basal Apparatus

45225.5 Response Elements Are Recognized by Activators

45425.6 There Are Many Types of DNA-Binding Domains

45625.7 A Zinc Finger Motif Is a DNA-Binding Domain

45825.8 Some Steroid Hormone Receptors Are Transcription Factors

45925.9 Zinc Fingers of Steroid Receptors Use a Combinatorial Code

46025.10 Binding to the Response Element Is Activated by Ligand Binding

46225.11 Homeodomains Bind Related Targets in DNA

46225.12 Helix-Loop-Helix Proteins Interact by Combinatorial Association

46425.13 Leucine Zippers Are Involved in Dimer Formation

46525.14 Summary

466

RNA Splicing and Processing

26

26.1 Introduction

46826.2 Nuclear Splice Junctions Are Short Sequences

46926.3 Splice Junctions Are Read in Pairs

47026.4 pre-mRNA Splicing Proceeds Through a Lariat

47 126.5 snRNAs Are Required for Splicing

473

26.6 U1 snRNP Initiates Splicing

47426.7 The E Complex Commits an RNA to Splicing

47526.8 5 snRNPs Form the Spliceosome

47626.9 Splicing Is Connected to Export of mRNA

47826.10 Group II Introns Autosplice via Lariat Formation

47926.11 Alternative Splicing Involves Differential Use of Splice Junctions

481

26.12 trans-Splicing Reactions Use Small RNAs

48226.13 Yeast tRNA Splicing Involves Cutting and Rejoining

48326.14 The 3' Ends of mRNAs Are Generated by Cleavage and Polyadenylation

48626.15 Small RNAs Are Required for rRNA Processing

48726.16 Summary

489

Catalytic RNA2

27.1 Introduction

49027.2

Group I Introns Undertake Self-Splicing by Transesterification

49127.3

Group I Introns Form a Characteristic Secondary Structure

49327.4

Ribozymes Have Various Catalytic Activities

49427.5

Some Group I Introns Code for Endonucleases that Sponsor Mobility

49627.6 Some Group II Introns Code for Reverse Transcriptases

49827.7

Some Autosplicing Introns Require Maturases

49927.8

Viroids Have Catalytic Activity

49927.9

RNA Editing Occurs at Individual Bases

50 127.10 RNA Editing Can Be Directed by Guide RNAs

50227.11 Protein Splicing Is Autocatalytic

50527.12 Summary

506

Part 6 The NucleusChromosomes

2828.1 Introduction

50728.2 Viral Genomes Are Packaged into Their Coats

50828.3 The Bacterial Genome Is a Supercoiled Nucleoid

51028.4 Eukaryotic DNA Has Loops and Domains Attached to a Scaffold

51228.5

Chromatin Is Divided into Euchromatin and Heterochromatin

51328.6 Chromosomes Have Banding Patterns

51 528.7 Lampbrush Chromosomes Are Extended

51 628.8 Polytene Chromosomes Form Bands That Puff at Sites of Gene Expression

51 728.9 Centromeres Often Have Extensive Repetitive DNA

51 928.10 S. cerevisiae Centromeres Have Short Protein-Binding DNA Sequences

52028.11 Telomeres Have Simple Repeating Sequences

52228.12 Telomeres Are Synthesized by a Ribonucleoprotein Enzyme

52328.13 Summary

525

Nucleosomes

2929.1 Introduction

52629.2 The Nucleosome Is the Subunit of all Chromatin

52729.3 DNA Is Coiled in Arrays of Nucleosomes

52829.4 Nucleosomes Have a Common Structure

52929.5 DNA Structure Varies on the Nucleosomal Surface

53029.6 The Nucleosome Absorbs Some Supercoiling

53229.7

Organization of the Core Particle

53329.8 The Path of Nucleosomes in the Chromatin Fiber

53429.9 Reproduction of Chromatin Requires Assembly of Nucleosomes

53529.10 Do Nucleosomes Lie at Specific Positions?

53829.11 Histone Octamers Are Displaced by Transcription

54029.12 DNAase Hypersensitive Sites Change Chromatin Structure

54229.13 Domains Define Regions that Contain Active Genes

54329.14 Insulators Block the Actions of Enhancers and Heterochromatin

54529.15 An LCR May Control a Domain

54729.16 What Constitutes a Regulatory Domain?

54829.17 Summary

549

Chromatin Structure Is a Focus for Regulation

30

30.1 Introduction

55030.2

Chromatin Remodeling Is an Active Process

55 130.3 There Are Several Chromatin Remodeling Complexes

55230.4 Nucleosome Organization May Be Changed at the Promoter

55430.5

Histone Modification Is a Key Event

55530.6

Histone Acetylation Occurs in Two Circumstances

55530.7 Acetylases Are Associated with Activators

55630.8 Deacetylases Are Associated with Repressors

55830.9 Methylation of Histones and DNA Is Connected

55830.10 Promoter Activation Is an Ordered Series of Events

55930.11 Histone Phosphorylation Affects Chromatin Structure

56030.12 Some Common Motifs Are Found in Proteins that Modify Chromatin

56 130.13 Heterochromatin Depends on Interactions with Histones

56230.14 Summary

564

Epigenetic Effects Are Inherited

31

31 .1 Introduction

56531 .2 Heterochromatin Propagates from a Nucleation Event

56631 .3

Polycomb and Trithorax Are Antagonistic Repressors and Activators

56831 .4 X Chromosomes Undergo Global Changes

57031 .5 DNA Methylation Is Perpetuated by a Maintenance Methylase

57231.6

DNA Methylation Is Responsible for Imprinting

57431.7 Yeast Prions Show Unusual Inheritance

57631.8 Prions Cause Diseases in Mammals

57831 .9 Summary

580

Genetic Engineering

3 2

32.1 Introduction

58132.2 Cloning Vectors Are Used to Amplify Donor DNA

58232.3 Cloning Vectors Can Be Specialized for Different Purposes

58532.4 Transfection Introduces Exogenous DNA into Cells

58732.5 Genes Can Be Injected into Animal Eggs

58932.6 ES Cells Can Be Incorporated into Embryonic Mice

59132.7 Gene Targeting Allows Genes to Be Replaced or Knocked Out

59232.8 Summary

594

Glossary G-1

Index I-1

Photo Credits

P-1