Molecular Biology of the Gene, Fifth Edition

by Watson, James D

• ISBN13: 9780805346350
• ISBN10: 080534635X
• Edition: 6th
• Format: Hardcover
• Copyright: 2003-12-23
• Publisher: Cold Spring Harbor Laboratory Press

Summary

The long-awaited new edition of James D. Watson's classic text,Molecular Biology of the Gene, has been thoroughly revised and is published to coincide with the 50th anniversary of Watson and Crick's paper on the structure of the DNA double-helix. Twenty-one concise chapters, co-authored by five highly respected molecular biologists, provide current, authoritative coverage of a fast-changing discipline, giving both historical and basic chemical context.Divided into four parts: Genetics and Chemistry, Central Dogma, Regulation, and Methods.For college instructors, students, and anyone interested in molecular biology and genetics.

Table of Contents

PART 1 CHEMISTRY AND GENETICS	1	(93)
The Mendelian View of the World	5	(14)
Mendel's Discoveries	6	(2)
The Principle of Independent Segregation	6	(1)
Mendelian Laws	6	(2)
Some Alleles Are Neither Dominant Nor Recessive	8	(1)
Principle of Independent Assortment	8	(1)
Chromosomal Theory of Heredity	8	(1)
Gene Linkage and Crossing Over	9	(3)
Genes Are Linked to Chromosomes	10	(2)
Chromosome Mapping	12	(3)
The Origin of Genetic Variability Through Mutations	15	(1)
Early Speculations about What Genes are and How they Act	16	(1)
Preliminary Attempts to Find a Gene-Protein Relationship	16	(3)
Summary	17	(1)
Bibliography	18	(1)
Nucleic Acids Convey Genetic Information	19	(22)
Avery's Bombshell: DNA can carry Genetic Specificity	20	(1)
Viral Genes are also Nucleic Acids	21	(1)
The Double Helix	21	(7)
Chargaff's Rules	23	(1)
Finding the Polymerases that Make DNA	24	(2)
Experimental Evidence Favors Strand Separation during DNA Replication	26	(2)
The Genetic Information within DNA is Conveyed by the Sequence of its Four Nucleotide Building Blocks	28	(3)
DNA Cannot Be the Template that Directly Orders Amino Acids during Protein Synthesis	28	(1)
Evidence that Genes Control Amino Acid Sequence in Proteins	29	(1)
RNA Is Chemically Very Similar to DNA	30	(1)
The Central Dogma	31	(6)
The Adaptor Hypothesis of Crick	31	(1)
The Test-Tube Synthesis of Proteins	32	(1)
The Paradox of the Nonspecific-Appearing Ribosomes	32	(1)
Discovery of Messenger RNA (mRNA)	33	(1)
Enzymatic Synthesis of RNA upon DNA Templates	33	(2)
Establishing the Genetic Code	35	(2)
Establishing the Direction of Protein Synthesis	37	(1)
Start and Stop Signals Are Also Encoded within DNA	38	(1)
The Era of Genomics	38	(3)
Summary	39	(1)
Bibliography	40	(1)
The Importance of Weak Chemical Interactions	41	(14)
Characteristics of Chemical Bonds	41	(3)
Chemical Bonds Are Explainable in Quantum-Mechanical Terms	42	(1)
Chemical-Bond Formation Involves a Change in the Form of Energy	43	(1)
Equilibrium between Bond Making and Breaking	43	(1)
The Concept of Free Energy	44	(1)
Keq Is Exponentially Related to ΔG	44	(1)
Covalent Bonds Are Very Strong	44	(1)
Weak Bonds in Biological Systems	45	(10)
Weak Bonds Have Energies between 1 and 7 kcal/mol	45	(1)
Weak Bonds Are Constantly Made and Broken at Physiological Temperatures	45	(1)
The Distinction between Polar and Nonpolar Molecules	45	(1)
Van der Waals Forces	46	(1)
Hydrogen Bonds	47	(1)
Some Ionic Bonds are Hydrogen Bonds	47	(1)
Weak Interactions Demand Complementary Molecular Surfaces	48	(1)
Water Molecules Form Hydrogen Bonds	49	(1)
Weak Bonds between Molecules in Aqueous Solutions	49	(1)
The Uniqueness of Molecular Shapes and the Concept of Selective Stickiness	50	(1)
Organic Molecules that Tend to Form Hydrogen Bonds are Water Soluble	51	(1)
Hydrophobic ``Bonds'' Stabilize Macromolecules	51	(1)
The Advantages of ΔG between 2 and 5 kcal/mol	52	(1)
Weak Bonds Attach Enzymes to Substrates	53	(1)
Weak Bonds Mediate Most Protein: DNA and Protein: Protein Interactions	53	(1)
Summary	53	(1)
Bibliography	54	(1)
The Importance of High-Energy Bonds	55	(14)
Molecules that Donate Energy are Thermodynamically Unstable	55	(2)
Enzymes lower Activation Energies in Biochemical Reactions	57	(1)
Free Energy in Biomolecules	58	(2)
High-Energy Bonds Hydrolyze with Large Negative ΔG	58	(2)
High-Energy Bonds in Biosynthetic Reactions	60	(1)
Peptide Bonds Hydrolyze Spontaneously	60	(1)
Coupling of Negative with Positive ΔG	61	(1)
Activation of Precursors in Group Transfer Reactions	61	(8)
ATP Versality in Group Transfer	62	(1)
Activation of Amino Acids by Attachment of AMP	63	(1)
Nucleic Acid Precursors are Activated by the Presence of P ~ P	64	(1)
The Value of P ~ P Release in Nucleic Acid Synthesis	64	(1)
P ~ P Splits Characterize Most Biosynthetic Reactions	65	(2)
Summary	67	(1)
Bibliography	67	(2)
Weak and Strong Bonds Determine Macromolecular Structure	69	(24)
Higher-Order Structures are Determined by Intra and Intermolecular Interactions	69	(9)
DNA Can Form a Regular Helix	69	(2)
RNA Forms a Wide Variety of Structures	71	(1)
Chemical Features of Protein Building Blocks	71	(1)
The Peptide Bond	72	(1)
Three Are Four Levels of Protein Structure	72	(2)
α Helices and β Sheets Are the Common Forms of Secondary Structure	74	(1)
Determination of Protein Structure	75	(3)
The Specific Conformation of a Protein Results from its Pattern of Hydrogen Bonds	78	(3)
α Helices Come Together to Form Coiled-Coils	80	(1)
Most Proteins are Modular, Containing Two or Three Domains	81	(3)
Proteins Are Composed of a Surprisingly Small Number of Structural Motifs	81	(1)
Large Proteins Are Often Constructed of Several Smaller Polypeptide Chains	82	(1)
Different Protein Functions Arise from Various Domain Combinations	82	(2)
Weak Bonds Correctly Position Proteins along DNA and RNA Molecules	84	(3)
Proteins Scan along DNA to Locate a Specific DNA-Binding Site	85	(1)
Diverse Strategies for Protein Recognition of RNA	86	(1)
Allostery: Regulation of a Protein's Function by Changing its Shape	87	(6)
The Structural Basis of Allosteric Regulation Is Known for Examples Involving Small Ligands, Protein-Protein Interactions, and Protein Modification	88	(3)
Not All Regulation of Proteins Is Mediated by Allosteric Events	91	(1)
Summary	91	(1)
Bibliography	92	(1)
PART 2 MAINTENANCE OF THE GENOME	93	(250)
The Structures of DNA and RNA	97	(32)
DNA Structure	98	(13)
DNA Is Composed of Polynucleotide Chains	98	(2)
Each Base Has Its Preferred Tautomeric Form	100	(1)
The Two Strands of the Double Helix Are Held Together by Base Pairing in an Antiparallel Orientation	100	(1)
The Two Chains of the Double Helix Have Complementary Sequences	101	(1)
Hydrogen Bonding Is Important for the Specificity of Base pairing	102	(1)
Bases Can Flip Out from the Double Helix	102	(1)
DNA Is Usually a Right-Handed Double Helix	103	(1)
The Double Helix Has Minor and Major Grooves	103	(1)
The Major Groove Is Rich in Chemical Information	103	(1)
DNA Has 10.5 Base Pairs per Turn of the Helix in Solution: The Mica Experiment	104	(2)
The Double Helix Exists in Multiple Conformations	106	(1)
DNA Can Sometimes Form a Left-Handed Helix	107	(1)
DNA Strands Can Separate (Denature) and Reassociate	108	(3)
Some DNA Molecules Are Circles	111	(1)
DNA Topology	111	(11)
Linking Number Is an Invariant Topological Property of Covalently Closed, Circular DNA	112	(1)
Linking Number Is Composed ot Twist and Writhe	112	(2)
Lk0 Is the Linking Number of Fully Relaxed cccDNA under Physiological Conditions	114	(1)
DNA in Cells Is Negatively Supercoiled	114	(1)
Nucleosomes Introduce Negative Supercoiling in Eukaryotes	115	(1)
Topoisomerases Can Relax Supercoiled DNA	115	(1)
Prokaryotes Have a Special Topoisomerase that Introduces Supercoils into DNA	116	(1)
Topoisomerases also Unknot and Disentangle DNA Molecules	117	(1)
Topoisomerases Use a Covalent Protein-DNA Linkage to Cleave and Rejoin DNA Strands	118	(1)
Topoisomerases Form an Enzyme Bridge and Pass DNA Segments through Each Other	118	(2)
DNA Topoisomers Can Be Separated by Electrophoresis	120	(1)
Ethidium Ions Cause DNA to Unwind	120	(1)
Proving that DNA Has a Helical Periodicity of about 10.5 Base Pairs per Turn from the Topological Properties of DNA Rings	121	(1)
RNA Structure	122	(7)
RNA Contains Ribose and Uracil and Is Usually Single-Stranded	122	(1)
RNA Chains Fold Back on Themselves to Form Local Regions of Double Helix Similar to A-Form DNA	123	(1)
RNA Can Fold Up into Complex Tertiary Structures	124	(1)
Some RNAs Are Enzymes	125	(1)
The Hammerhead Ribozyme Cleaves RNA by the Formation of a 2',3' Cyclic Phosphate	125	(1)
Did Life Evolve from an RNA World?	126	(1)
Summary	126	(1)
Bibliography	127	(2)
Chromosomes, Chromatin, and the Nucleosome	129	(52)
Chromosome Sequence and Diversity	130	(8)
Chromosomes Can Be Circular or Linear	130	(1)
Every Cell Maintains a Characteristic Number of Chromosomes	131	(2)
Genome Size Is Related to the Complexity of the Organism	133	(1)
The E. coli Genome Is Composed almost Entirely of Genes	134	(1)
More Complex Organisms Have Decreased Gene Density	134	(1)
Genes Make Up Only a Small Proportion of the Eukaryotic Chromosomal DNA	135	(2)
The Majority of Human Intergenic Sequences Are Composed of Repetitive DNA	137	(1)
Chromosome Duplication and Segregation	138	(13)
Eukaryotic Chromosomes Require Centromeres, Telomeres, and Origins of Replication to Be Maintained during Cell Division	138	(3)
Eukaryotic Chromosome Duplication and Segregation Occur in Separate Phases of the Cell Cycle	141	(2)
Chromosome Structure Changes as Eukaryotic Cells Divide	143	(1)
Sister Chromatid Cohesion and Chromosome Condensation Are Mediated by SMC Proteins	144	(2)
Mitosis Maintains the Parental Chromosome Number	146	(1)
The Gap Phases of the Cell Cycle Allow Time to Prepare for the Next Cell Cycle Stage while also Checking that the Previous Stage Is Finished Correctly	146	(2)
Meiosis Reduces the Parental Chromosome Number	148	(2)
Different Levels of Chromosome Structure Can Be Observed by Microscopy	150	(1)
The Nucleosome	151	(9)
Nucleosomes Are the Building Blocks of Chromosomes	151	(1)
Micrococcal Nuclease and the DNA Associated with the Nucleosome	152	(1)
Histones Are Small, Positively-Charged Proteins	153	(1)
The Atomic Structure of the Nucleosome	154	(2)
Many DNA Sequence-Independent Contacts Mediate the Interaction between the Core Histones and DNA	156	(3)
The Histone N-Terminal Tails Stabilize DNA Wrapping around the Octamer	159	(1)
Higher-Order Chromatin Structure	160	(5)
Histone H1 Binds to the Linker DNA between Nucleosomes	160	(1)
Nucleosome Arrays Can Form More Complex Structures: the 30-nm Fiber	161	(1)
The Histone N-Terminal Tails Are Required for the Formation of the 30-nm Fiber	162	(1)
Further Compaction of DNA Involves Large Loops of Nucleosomal DNA	162	(1)
Histone Variants Alter Nucleosome Function	163	(2)
Regulation of Chromatin Structure	165	(10)
The Interaction of DNA with the Histone Octamer Is Dynamic	165	(1)
Nucleosome Remodeling Complexes Facilitate Nucleosome Movement	166	(2)
Some Nucleosomes Are Found in Specific Positions in vivo: Nucleosome Positioning	168	(1)
Modification of the N-Terminal Tails of the Histones Alters Chromatin Accessibility	169	(1)
Determining Nucleosome Position in the Cell	170	(3)
Specific Enzymes Are Responsible for Histone Modification	173	(1)
Nucleosome Modification and Remodeling Work Together to Increase DNA Accessibility	174	(1)
Nucleosome Assembly	175	(6)
Nucleosomes Are Assembled Immediately after DNA Replication	175	(1)
Assembly of Nucleosomes Requires Histone ``Chapterones''	176	(3)
Summary	179	(1)
Bibliography	180	(1)
The Replication of DNA	181	(54)
The Chemistry of DNA Synthesis	182	(2)
DNA Synthesis Requires Deoxynucleoside Triphosphates and a Primer: Template Junction	182	(1)
DNA Is Synthesized by Extending the 3' End of the Primer	183	(1)
Hydrolysis of Pyrophosphates Is the Driving Force for DNA Synthesis	183	(1)
The Mechanism of DNA Polymerase	184	(8)
DNA Polymerases Use a Single Active Site to Catalyze DNA Synthesis	184	(2)
DNA Polymerases Resemble a Hand that Grips the Primer: Template Junction	186	(2)
DNA Polymeras Are Processive Enzymes	188	(3)
Exonucleases Proofread Newly Synthesized DNA	191	(1)
The Replication Fork	192	(8)
Both Strands of DNA Are Synthesized Together at the Replication Fork	192	(1)
The Initiation of a New Strand of DNA Requires an RNA Primer	193	(1)
RNA Primers Must Be Removed to Complete DNA Replication	194	(1)
DNA Helicases Unwind the Double Helix in Advance of the Replication Fork	194	(1)
Single-Stranded Binding Proteins Stabilize Single-Stranded DNA Prior to Replication	195	(1)
Determining the Polarity of a DNA Helicase	196	(2)
Topoisomerases Remove Supercoils Produced by DNA Unwinding at the Replication Fork	198	(1)
Replication Fork Enzymes Extend the Range of DNA Polymerase Substrates	199	(1)
The Specialization of DNA Polymerases	200	(5)
DNA Polymerases Are Specialized for Different Roles in the Cell	200	(1)
Sliding Clamps Dramatically Increase DNA Polymerase Processivity	201	(3)
Sliding Clamps Are Opened and Placed on DNA by Clamps Loaders	204	(1)
DNA Synthesis at the Replication Fork	205	(7)
ATP Control of Protein Function: Loading a Sliding Clamp	206	(4)
Interactions between Replication Fork Proteins Form the E. coli Replisome	210	(2)
Initiation of DNA Replication	212	(2)
Specific Genomic DNA Sequences Direct the Initiation of DNA Replication	212	(1)
The Replicon Model of Replication Initiation	212	(1)
Replicator Sequences Include Initiator Binding Sites and Easily Unwound DNA	213	(1)
Binding and Unwinding: Origin Selection and Activation By the Initiator Protein	214	(14)
The Identification of Origins of Replication and Replicators	214	(3)
Protein-Protein and Protein-DNA Interactions Direct the Initiation Process	217	(1)
E. coli DNA Replication Is Regulated by DNA-ATP Levels and SeqA	217	(4)
The Replication Factory Hypothesis	221	(2)
Eukaryotic Chromosomes Are Replicated Exactly Once per Cell Cycle	223	(1)
Pre-Replicative Complex Formation Directs the Initiation of Replication in Eukaryotes	223	(2)
Pre-RC Formation and Activation Is Regulated to Allow only a Single Round of Replication during Each Cell Cycle	225	(3)
Similarities between Eukaryotic and Prokaryotic DNA Replication Initiation	228	(1)
Finishing Replication	228	(7)
Type II Topoisomerases Are Required to Separate Daughter DNA Molecules	228	(1)
Lagging Strand Synthesis Is Unable to Copy the Extreme Ends of Linear Chromosomes	229	(1)
Telomerase Is a Novel DNA Polymerase that Does Not Require an Exogenous Template	230	(2)
Telomerase Solves the End Replication Problem by Extending the 3' End of the Chromosome	232	(1)
Summary	232	(1)
Bibliography	233	(2)
The Mutability and Repair of DNA	235	(24)
Replication Errors and Their Repair	236	(6)
The Nature of Mutations	236	(1)
Some Replication Errors Escape Proofreading	237	(1)
Expansion of Triple Repeats Causes Disease	237	(1)
Mismatch Repair Removes Errors that Escape Proofreading	238	(4)
DNA Damage	242	(4)
DNA Undergoes Damage Spontaneously from Hydrolysis and Deamination	242	(1)
The Ames Test	243	(1)
DNA Is Damaged by Alkylation, Oxidation, and Radiation	244	(1)
Mutations Are also Caused by Base Analogs and Intercalating Agents	245	(1)
Repairs of DNA Damage	246	(13)
Direct Reversal of DNA Damage	247	(1)
Base Excision Repair Enzymes Remove Damaged Bases by a Base-Flipping Mechanism	248	(2)
Nucleotide Excision Repair Enzymes Cleave Damaged DNA on Either Side of the Lesion	250	(3)
Recombination Repairs DNA Breaks by Retrieving Sequence Information from Undamaged DNA	253	(1)
Translesion DNA Synthesis Enables Replication to Proceed across DNA Damage	254	(2)
The Y-Family of DNA Polymerases	256	(1)
Summary	257	(1)
Bibliography	258	(1)
Homologous Recombination at the Molecular Level	259	(34)
Models for Homologous Recombination	259	(9)
The Holiday Model Illustrates Key Steps in Homologous Recombination	260	(4)
The Double-Strand Break Repair Model More Accurately Describes Many Recombination Events	264	(2)
How to Resolve a Recombination Intermediate with Two Holliday Junctions	266	(1)
Double-Stranded DNA Breaks Arise by Numerous Means and Initiate Homologous Recombination	267	(1)
Homologous Recombination Protein Machines	268	(10)
The RecBCD Helicase/Nuclease Processes Broken DNA Molecules for Recombination	269	(3)
RecA Protein Assembles on Single-Stranded DNA and Promotes Strand Invasion	272	(2)
Newly Base-Paired Partners Are Established within the RecA Filament	274	(1)
RecA Homologs Are Present in All Organisms	275	(1)
RuvAB Complex Specifically Recognizes Holliday Junctions and Promotes Branch Migration	276	(1)
RuvC Cleaves Specific DNA Strands at the Holliday Junction to Finish Recombination	276	(2)
Homologous Recombination in Eukaryotes	278	(7)
Homologous Recombination Has Additional Functions in Eukaryotes	278	(1)
Homologous Recombination Is Required for Chromosome Segregation during Meiosis	279	(1)
Programmed Generation of Double-Stranded DNA Breaks Occurs during Meiosis	279	(3)
MRX Protein Processes the Cleaved DNA Endsfor Assembly of the RecA-like Strand-Exchange Proteins	282	(1)
Dmcl Is a RecA-like Protein that Specifically Functions in Meiotic Recombination	282	(2)
Many Proteins Function Together to Promote Meiotic Recombination	284	(1)
Mating-Type Switching	285	(3)
Mating-Type Switching Is Initiated by a Site-Specific Double-Strand Break	286	(1)
Mating-Type Switching Is a Gene Conversion Event, Not Associated with Crossing Over	286	(2)
Genetic Consequences of the Mechanism of Homologous Recombination	288	(5)
Gene Conversion Occurs because DNA Is Repaired during Recombination	289	(1)
Summary	290	(1)
Bibliography	291	(2)
Site-Specific Recombination and Transposition of DNA	293	(50)
Conservative Site-Specific Recombination	294	(8)
Site-Specific Recombination Occurs at Specific DNA Sequences in the Target DNA	294	(2)
Site-Specific Recombinases Cleave and Rejoin DNA Using a Covalent Protein-DNA Intermediate	296	(2)
Serine Recombinases Introduce Double-Stranded Breaks in DNA and then Swap Strands to Promote Recombination	298	(1)
Tyrosine Recombinases Break and Rejoin One Pair of DNA Strands at a Time	299	(1)
Structures of Tyrosine Recombinases Bound to DNA Reveal the Mechanism of DNA Exchange	300	(2)
Application of Site-Specific Recombination to Genetic Engineering	302	(1)
Biological Roles of Site-Specific Recombination	302	(8)
λ Integrase Promotes the Integration and Excision of a Viral Genome into the Host Cell Chromosome	303	(1)
Phage λ Excision Requires a New DNA-Bending Protein	304	(1)
The Hin Recombinase Inverts a Segment of DNA Allowing Expression of Alternative Genes	305	(1)
Hin Recombination Requires a DNA Enhancer	306	(1)
Recombinases Convert Multimeric Circular DNA Molecules into Monomers	307	(3)
There Are Other Mechanisms to Direct Recombination to Specific Segments of DNA	310	(1)
Transposition	310	(17)
Some Genetic Elements Move to New Chromosomal Locations by Transposition	310	(1)
There Are Three Principal Classes of Transposable Elements	311	(1)
DNA Transposons Carry a Transposase Gene, Flanked by Recombination Sites	312	(1)
Transposons Exist as Both Autonomous and Nonautonomous Elements	313	(1)
Viral-like Retrotransposons and Retroviruses Carry Terminal Repeat Sequences and Two Genes Important for Recombination	313	(1)
Poly-A Retrotransposons Look Like Genes	314	(1)
DNA Transposition by a Cut-and-Paste Mechanism	314	(2)
The Intermediate in Cut-and-Paste Transposition Is Finished by Gap Repair	316	(1)
There Are Multiple Mechanisms for Cleaving the Nontransferred Strand during DNA Transposition	316	(2)
DNA Transposition by a Replicative Mechanism	318	(2)
Viral-like Retrotransposons and Retroviruses Move Using an RNA Intermediate	320	(1)
DNA Transposases and Retroviral Integrases Are Members of a Protein Superfamily	321	(1)
The Pathway of Retroviral cDNA Formation	322	(2)
Poly-A Retrotransposons Move by a ``Reverse Splicing'' Mechanism	324	(3)
Examples of Transposable Elements and Their Regulation	327	(10)
IS4-Family Transposons Are Compact Elements with Multiple Mechanisms for Copy Number Control	327	(1)
Maize Elements and the Discovery of Transposons	328	(1)
Tn10 Transposition Is Coupled to Cellular DNA Replication	329	(2)
Phage Mu Is an Extremely Robust Transposon	331	(1)
Mu Uses Target Immunity to Avoid Transposing into Its Own DNA	331	(3)
Tc1/Mariner Elements Are Extremely Successful DNA Elements in Eukaryotes	334	(1)
Yeast Ty Elements Transpose into Safe Havens in the Genome	335	(1)
LINEs Promote Their Own Transposition and Even Transpose Cellular RNAs	336	(1)
V(D)J Recombination	337	(6)
The Early Events in V(D)J Recombination Occur by a Mechanism Similar to Transposon Excision	339	(3)
Summary	342	(1)
Bibliography	342	(1)
PART 3 EXPRESSION OF THE GENOME	343	(136)
Mechanisms of Transcription	347	(32)
RNA Polymerases And the Transcription Cycle	348	(5)
RNA Polymerases Come in Different Forms, but Share Many Features	348	(2)
Transcription by RNA Polymerase Proceeds in a Series of Steps	350	(2)
Transcription Initiation Involves Three Defined Steps	352	(1)
The Transcription Cycle in Bacteria	353	(10)
Bacterial Promoters Vary in Strength and Sequence, but Have Certain Defining Features	353	(1)
The σ Factor Mediates Binding of Polymerase to the Promoter	354	(1)
Consensus Sequences	355	(1)
Transition to the Open Complex Involves Structural Changes in RNA Polymerase and in the Promoter DNA	356	(2)
Transcription Is Initiated by RNA Polymerase without the Need for a Primer	358	(1)
RNA Polymerase Synthesizes Several Short RNAs before Entering the Elongation Phase	358	(1)
The Elongating Polymerase Is a Processive Machine that Synthesizes and Proofreads RNA	359	(1)
The Single-Subunit RNA Polymerases	360	(1)
Transcription Is Terminated by Singals within the RNA Sequence	361	(2)
Transcription in Eukaryotes	363	(16)
RNA Polymerase II Core Promoters Are Made up of Combinations of Four Different Sequence Elements	363	(1)
RNA Polymerase II Forms a Pre-Initiation Complex with General Transcription Factors at the Promoter	364	(2)
TBP Binds to and Distorts DNA Using a β Sheet Inserted into the Minor Groove	366	(1)
The Other General Transcription Factors also Have Specific Roles in Initiation	367	(1)
In Vivo, Transcription Initiation Requires Additional Proteins, Including the Mediator Complex	368	(1)
Mediator Consists of Many Subunits, Some Conserved from yeast to Human	369	(1)
A New Set of Factors Stimulate Pol II Elongation and RNA Proofreading	370	(1)
Elongating Polymerase Is Associated with a New Set of Protein Factors Required for Various Types of RNA Processing	371	(3)
RNA Polymerases I and III Recognize Distinct Promoters, Using Distinct Sets of Transcription Factors, but still Require TBP	374	(2)
Summary	376	(1)
Bibliography	377	(2)
RNA Splicing	379	(32)
The Chemistry of RNA Splicing	380	(3)
Sequences within the RNA Determine Where Splicing Occurs	380	(1)
The Intron Is Removed in a Form Called a Lariat as the Flanking Exons Are Joined	381	(2)
Exons from Different RNA Molecules Can Be Fused by Trans-Splicing	383	(1)
The Spliceosome Machinery	383	(2)
RNA Splicing Is Carried Out by a Large Complex Called the Spliceosome	383	(2)
Splicing Pathways	385	(9)
Assembly, Rearrangements, and Catalysis Within the Spliceosome: the Splicing Pathway	385	(2)
Self-Splicing Introns Reveal that RNA Can Catalyze RNA Splicing	387	(1)
Group I Introns Release a Linear Intron Rather than a Lariat	388	(1)
Converting Group I Introns into Ribozymes	389	(2)
How Does the Spliceosome Find the Splice Sites Reliably?	391	(3)
Alternative Splicing	394	(7)
Single Genes Can Produce Multiple Products by Alternative Splicing	394	(2)
Alternative Splicing Is Regulated by Activators and Repressors	396	(2)
Adenovirus and the Discovery of Splicing	398	(2)
A Small Group of Introns Are Spliced by an Alternative Spliceosome Composed of a Different Set of snRNPs	400	(1)
Exon Shuffling	401	(3)
Exons Are Shuffled by Recombination to Produce Genes Encoding New Proteins	400	(4)
RNA Editing	404	(2)
RNA Editing Is Another Way of Altering the Sequence of an mRNA	404	(2)
mRNA Transport	406	(5)
Once Processed, mRNA Is Packaged and Exported from the Nucleus into the Cytoplasm for Translation	406	(2)
Summary	408	(1)
Bibliography	409	(2)
Translation	411	(50)
Messenger RNA	412	(3)
Polypeptide Chains Are Specified by Open-Reading Frames	412	(1)
Prokaryotic mRNAs Have a Ribosome Binding Site that Recruits the Translational Machinery	413	(1)
Eukaryotic mRNAs Are Modified at Their 5' and 3' Ends to Facilitate Translation	414	(1)
Transfer RNA	415	(2)
tRNAs Are Adaptors between Codons and Amino Acids	415	(1)
tRNAs Share a Common Secondary Structure that Resembles a Cloverleaf	416	(1)
tRNAs Have an L-Shaped Three-Dimensional Structure	417	(1)
Attachment of Amino Acids to tRNA	417	(6)
tRNAs Are Charged by the Attachment of an Amino Acid to the 3' Terminal Adenosine Nucleotide via a High-Energy Acyl Linkage	417	(1)
Aminoacyl tRNA Synthetases Charge tRNAs in Two Steps	418	(1)
Each Aminoacyl tRNA Synthetase Attaches a Single Amino Acid to One or More tRNAs	419	(1)
tRNA Synthetases Recognize Unique Structural Features of Cognate tRNAs	420	(1)
Aminoacyl-tRNA Formation Is Very Accurate	421	(1)
Some Aminoacyl tRNA Synthetases Use an Editing Pocket to Charge tRNAs with High Accuracy	422	(1)
The Ribosome Is Unable to Discriminate between Correctly and Incorrectly Charged tRNAs	422	(1)
Selenocysteine	423	(1)
The Ribosome	423	(9)
The Ribosome Is Composed of a Large and a Small Subunit	425	(1)
The Large and Small Subunits Undergo Association and Dissociation during each Cycle of Translation	425	(2)
New Amino Acids Are Attached to the C-Terminus of the Growing Polypeptide Chain	427	(1)
Peptide Bonds Are Formed by Transfer of the Growing Polypeptide Chain from One tRNA to Another	428	(1)
Ribosomal RNAs Are Both Structural and Catalytic Determinats of the Ribosome	428	(1)
The Ribosome Has Three Binding Sites for tRNA	429	(1)
Channels through the Ribosome Allow the mRNA and Growing Polypeptide to Enter and/or Exit the Ribosome	430	(2)
Initiation of Translation	432	(8)
Prokaryotic mRNAs Are Initially Recruited to the Small Subunit by Base-Pairing to rRNA	433	(1)
A Specialized tRNA Charged with a Modified Methionine Binds Directly to the Prokaryotic Small Subunit	433	(1)
Three Initiation Factors Direct the Assembly of an Initiation Complex that Contains mRNA and the Initiator tRNA	433	(2)
Eukaryotic Ribosomes Are Recruited to the mRNA by the 5' Cap	435	(2)
The Start Codon Is Found by Scanning Downstream from the 5' End of the mRNA	437	(1)
Translation Initiation Factors Hold Eukaryotic mRNAs in Circles	438	(1)
uORFs and IRESs: Exceptions that Prove the Rule	439	(1)
Translation Elongation	440	(8)
Aminoacyl-tRNAs Are Delivered to the A Site by Elongation Factor EF-Tu	441	(1)
The Ribosome Uses Multiple Mechanisms to Select Against Incorrect Aminoacyl-tRNAs	441	(1)
The Ribosome Is a Ribozyme	442	(2)
Peptide Bond Formation and the Elongation Factor EF-G Drive Translocation of the tRNAs and the mRNA	444	(1)
EF-G Drives Translocation by Displacing the tRNA Bound to the A Site	445	(1)
EF-Tu-GDP and EF-G-GDP Must Exchange GDP for GTP Prior to Participating in a New Round of Elongation	446	(1)
A Cycle of Peptide Bond Formation Consumes Two Molecules of GTP and One Molecule of ATP	446	(1)
GTP-Binding Proteins, Conformational Switching, and the Fidelity and Ordering of the Events of Translation	447	(1)
Termination of Translation	448	(4)
Release Factors Terminate Translation in Response to Stop Codons	448	(1)
Short Regions of Class I Release Factors Recognize Stop Codons and Trigger Release of the Peptidyl Chain	449	(1)
GDP/GTP Exchange and GTP Hydrolysis Control the Function of the Class II Release Factor	450	(1)
The Ribosome Recycling Factor Mimics a tRNA	450	(2)
Translation-Dependent Regulation of mRNA and Protein Stability	452	(9)
The SsrA RNA Rescues Ribosomes that Translate Broken mRNAs	452	(1)
Antibiotics Arrest Cell Division by Blocking Specific Steps in Translation	453	(3)
Eukaryotic Cells Degrade mRNAs that Are Incomplete or that Have Premature Stop Codons	456	(2)
Summary	458	(1)
Bibliography	459	(2)
The Genetic Code	461	(18)
The Code is Degenerate	461	(8)
Perceiving Order in the Makeup of the Code	462	(1)
Wobble in the Anticodon	463	(1)
Three Codons Direct Chain Termination	463	(1)
How the Code Was Cracked	464	(1)
Stimulation of Amino Acid Incorporation by Synthetic mRNAs	465	(1)
Poly-U Codes for Polyphenylalanine	466	(1)
Mixed Copolymers Allowed Additional Codon Assignments	467	(1)
Transfer RNA Binding to Defined Trinucleotide Codons	468	(1)
Codon Assignments from Repeating Copolymers	468	(1)
Three Rules Govern the Genetic Code	469	(2)
Three Kinds of Point Mutations Alter the Genetic Code	470	(1)
Genetic Proof that the Code Is Read in Units of Three	471	(1)
Suppressor Mutations Can Reside in the Same or a Different Gene	471	(4)
Intergenic Suppression Involves Mutant tRNAs	472	(2)
Nonsense Suppressors also Read Normal Termination Signals	474	(1)
Proving the Validity of the Genetic Code	474	(1)
The Code is Nearly Universal	475	(4)
Summary	477	(1)
Bibliography	477	(2)
PART 4 REGULATION	479	(164)
Gene Regulation in Prokaryotes	483	(46)
Principles of Transcriptional Regulation	483	(5)
Gene Expression Is Controlled by Regulatory Proteins	483	(1)
Many Promoters Are Regulated by Activators that Help RNA Polymerase Bind DNA and by Repressors that Block that Binding	484	(1)
Some Activators Work by Allostery and Regulate Steps after RNA Polymerase Binding	485	(1)
Action at a Distance and DNA Looping	486	(1)
Cooperative Binding and Allostery Have Many Roles in Gene Regulation	487	(1)
Antitermination and Beyond: Not All of Gene Regulation Targets Transcription Initiation	487	(1)
Regulation of Transcription Initiation: Examples from Bacteria	488	(16)
An Activator and a Repressor Together Control the lac Genes	488	(1)
CAP and Lac Repressor Have Opposing Effects on RNA Polymerase Binding to the lac Promoter	489	(1)
Detecting DNA-Binding Sites	490	(2)
CAP Has Separate Activating and DNA-Binding Surfaces	492	(1)
CAP and Lac Repressor Bind DNA Using a Common Structural Motif	493	(1)
Activator Bypass Experiments	493	(3)
The Activities of Lac Repressor and CAP Are Controlled Allosterically by Their Signals	496	(1)
Jacob, Monod, and the Ideas Behind Gene Regulation	497	(2)
Combinatorial Control: CAP Controls Other Genes As Well	499	(1)
Alternative σ Factors Direct RNA Polymerase to Alternative Sets of Promoters	499	(1)
NtrC and MerR: Transcriptional Activators that Work by Allostery Rather than by Recruitment	500	(1)
NtrC Has ATPase Activity and Works from DNA Sites Far from the Gene	500	(1)
MerR Activates Transcription by Twisting Promoter DNA	501	(1)
Some Repressors Hold RNA Polymerase at the Promoter Rather than Excluding It	502	(1)
AraC and Control of the araBAD Operon by Antiactivation	503	(1)
Examples of Gene Regulation at Steps After Transcription Initiation	504	(8)
Amino Acid Biosynthetic Operons Are Controlled by Premature Transcription Termination	504	(2)
Ribosomal Proteins Are Translational Repressors of Their Own Synthesis	506	(3)
Riboswitches	509	(3)
The Case of Phage λ: Layers of Regulation	512	(17)
Alternative Patterns of Gene Expression Control Lytic and Lysogenic Growth	513	(1)
Regulatory Proteins and Their Binding Sites	514	(1)
λ Repressor Binds to Operator Sites Cooperatively	515	(1)
Concentration, Affinity, and Cooperative Binding	516	(1)
Repressor and Cro Bind in Different Patterns to Control Lytic and Lysogenic Growth	517	(1)
Lysogenic Induction Requires Proteolytic Cleavage of λ Repressor	518	(1)
Negative Autoregulation of Repressor Requires Long-Distance Interactions and a Large DNA Loop	519	(1)
Another Activator, λcII, Controls the Decision between Lytic and Lysogenic Growth upon Infection of a New Host	520	(1)
Genetic Approaches that Identified Genes Involved in the Lytic/Lysogenic Choice	521	(1)
Growth Conditions of E. coli Control the Stability of CII Protein and thus the Lytic/Lysogenic Choice	522	(1)
Transcriptional Antitermination in λ Development	523	(1)
Retroregulation: An Interplay of Controls on RNA Synthesis and Stability Determines in Gene Expression	524	(1)
Summary	525	(1)
Bibliography	526	(3)
Gene Regulation in Eukaryotes	529	(46)
Conserved Mechanisms of Transcriptional Regulation from Yeast to Mammals	531	(6)
Activators Have Separate DNA Binding and Activating Functions	531	(2)
The Two Hybrid Assay	533	(1)
Eukaryotic Regulators Use a Range of DNA-Binding Domains, but DNA Recognition Involves the Same Principles as Found in Bacteria	534	(2)
Activating Regions Are Not Well-Defined Structures	536	(1)
Recruitment of Protein Complexes to Genes By Eukaryotic Activators	537	(7)
Activators Recruit the Transcriptional Machinery to the Gene	537	(2)
Chromatin Immunoprecipitation	539	(1)
Activators also Recruit Nucleosome Modifiers that Help the Transcription Machinery Bind at the Promoter	540	(1)
Action at a Distance: Loops and Insulators	540	(3)
Appropriate Regulation of Some Groups of Genes Requires Locus Control Regions	543	(1)
Signal Integration and Combinatorial Control	544	(5)
Activators Work Together Synergistically to Integrate Signals	544	(2)
Signal Integration: the HO Gene Is Controlled by Two Regulators; One Recruits Nucleosome Modifiers and the Other Recruits Mediator	546	(1)
Signal Integration: Cooperative Binding of Activators at the Human β-Interferon Gene	546	(1)
Combinatorial Control Lies at the Heart of the Complexity and Diversity of Eukaryotes	547	(1)
Combinatorial Control of the Mating-Type Genes from Saccharomyces cerevisiae	548	(1)
Transcriptional Repressors	549	(2)
Signal Transduction and the Control of Transcriptional Regulators	551	(5)
Signals Are Often Communicated to Transcriptional Regulators through Signal Transduction Pathways	551	(1)
Signals Control the Activities of Eukaryotic Transcriptional Regulators in a Variety of Ways	552	(3)
Activators and Repressors Sometimes Come in Pieces	555	(1)
Gene ``Silencing'' by Modification of Histones and DNA	556	(6)
Silencing in Yeast is Mediated by Deacetylation and Methylation of Histones	556	(2)
Histone Modifications and the Histone Code Hypothesis	558	(1)
DNA Methylation Is Associated with Silenced Genes in Mammalian Cells	558	(2)
Some States of Gene Expression Are Inherited through Cell Division even when the Initiating Signal Is No Longer Present	560	(2)
λ Lysogens and the Epigenetic Switch	562	(1)
Eukaryotic Gene Regulation at Steps After Transcription Initiation	562	(5)
Some Activators Control Transcriptional Elongation rather than Initiation	562	(1)
The Regulation of Alternative mRNA Splicing Can Produce Different Protein Products in Different Cell Types	563	(2)
Expression of the Yeast Transcriptional Activator Gcn4 Is Controlled at the Level of Translation	565	(2)
RNAS in Gene Regulation	567	(8)
Double-Stranded RNA Inhibits Expression of Genes Homologous to that RNA	568	(1)
Short Interfering RNAs (siRNAs) Are Produced from dsRNA and Direct Machinery that Switches Off Genes in Various Ways	568	(2)
MicroRNAs Control the Expression of some Genes during Development	570	(1)
Summary	571	(1)
Bibliography	572	(3)
Gene Regulation during Development	575	(38)
Three Strategies by which Cells are Instructed to Express Specific Sets of Genes During Development	576	(4)
Some mRNAs Become Localized within Eggs and Embroys due to an Intrinsic Polarity in the Cytoskeleton	576	(1)
Cell-to-Cell Contact and Secreted Cell Signaling Molecules both elicit Changes in Gene Expression in Neighboring Cells	576	(1)
Microarray Assays: Theory and Practice	577	(1)
Gradients of Secreted Signaling Molecules Can Instruct Cells to Follow Different Pathways of Development based on Their Location	578	(2)
Examples of the Three Strategies for Establishing Differential Gene Expression	580	(10)
The Localized Ash 1 Repressor Controls Mating Type in Yeast by Silencing the HO Gene	580	(2)
Review of Cytoskeleton: Asymmetry and Growth	582	(2)
A Localized mRNA Initiates Muscle Differentiation in the Sea Squirt Embryo	584	(1)
Cell-to-Cell Contact Elicits Differential Gene Expression in the Sporulating Bacterium, B. subtilis	584	(1)
Overview of Ciona Development	585	(2)
A Skin-Nerve Regulatory Switch Is Controlled by Notch Signaling in the Insect CNS	587	(1)
A Gradient of the Sonic Hedgehog Morphogen Controls the Formation of Different Neurons in the Vertebrate Neural Tube	588	(2)
The Molecular Biology of Drosophila Embryogenesis	590	(23)
An Overview of Drosophila Embryogenesis	590	(1)
A Morphogen Gradient Controls Dorsal-Ventral patterning of the Drosophila Embryo	590	(2)
Overview of Drosophila Development	592	(5)
The Role of Activator Synergy in Development	597	(2)
Segmentation Is Initiated by Localized RNAs at the Anterior and Posterior Poles of the Unfertilized Egg	599	(2)
The Bicoid Gradient Regulates the Expression of Segmentation Genes in a Concentration-Dependent Fashion	601	(1)
Hunchback Expression Is also Regulated at the Level of Translation	602	(1)
The Gradient of Hunchback Repressor Establishes Different Limits of Gap Gene Expression	603	(1)
Hunchback and Gap Proteins Produce Segmentation Stripes of Gene Expression	604	(1)
Bioinformatics Methods for Identification of Complex Enhancers	605	(2)
Gap Repressor Gradients Produce many Stripes of Gene Expression	607	(1)
Short-Range Transcriptional Repressors Permit Different Enhancers to Work Independently of one Another within the Complex eve Regulatory Region	608	(1)
Summary	609	(1)
Bibliography	610	(3)
Comparative Genomics and the Evolution of Animal Diversity	613	(30)
Most Animals Have Essentially The Same Genes	614	(5)
How Does Gene Duplication Give Rise to Biological Diversity?	616	(1)
Gene Duplication and the Importance of Regulatory Evolution	616	(2)
Duplication of Globin Genes Produces New Expression Patterns and Diverse Protein Functions	618	(1)
Creation of New Genes Drives Bacterial Evolution	618	(1)
Three Ways Gene Expression is Changed During Evolution	619	(1)
Experimental Manipulations that Alter Animal Morphology	620	(10)
Changes in Pax6 Expression Create Ectopic Eyes	621	(1)
Changes in Antp Expression Transform Antennae into Legs	622	(1)
Importance of Protein Function: Interconversion of ftz and Antp	622	(1)
Subtle Changes in an Enhancer Sequence Can Produce New Patterns of Gene Expression	623	(1)
The Misexpression of Ubx Changes the Morphology of the Fruit Fly	624	(2)
Changes in Ubx Function Modify the Morphology of Fruit Fly Embryos	626	(1)
Changes in Ubx Target Enchancers Can Alter Patterns of Gene Expression	627	(1)
The Homeotic Genes of Drosophila Are Organized in Special Chromosome Clusters	627	(3)
Morphological Changes in Crustaceans and Insects	630	(5)
Arthropods Are Remarkably Diverse	630	(1)
Changes in Ubx Expression Explain Modifications in Limbs among the Crustaceans	630	(1)
Why Insects Lack Abdominal Limbs	631	(1)
Modification of Flight Limbs Might Arise from the Evolution of Regulatory DNA Sequences	632	(1)
Co-option of Gene Networks for Evolutionary Innovation	633	(2)
Genome Evolution and Human Origins	635	(8)
Humans Contain Surprisingly Few Genes	635	(1)
The Human Genome Is very Similar to that of the Mouse and Virtually Identical to the Chimp	636	(1)
The Evolutionary Origins of Human Speech	637	(1)
How FOXP2 Fosters Speech in Humans	637	(1)
The Future of Comparative Genome Analysis	638	(1)
Summary	639	(1)
Bibliography	640	(3)
PART 5 METHODS	643	(70)
Techniques of Molecular Biology	647	(34)
Introduction	647	(1)
Nucleic Acids	648	(24)
Electrophoresis through a Gel Separates DNA and RNA Molecules According to Size	648	(1)
Restriction Endonucleases Cleave DNA Molecules at Particular Sites	649	(2)
DNA Hybridization Can Be Used to Identify Specific DNA Molecules	651	(1)
Hybridization Probes Can Identify Electrophoretically-Separated DNAs and RNAs	652	(1)
Isolation of Specific Segments of DNA	653	(1)
DNA Cloning	654	(1)
Cloning DNA in Plasmid Vectors	654	(1)
Vector DNA Can Be Introduced into Host Organisms by Transformation	655	(1)
Libraries of DNA Molecules Can Be Created by Cloning	656	(1)
Hybridization Can Be Used to Identify a Specific Clone in a DNA Library	657	(1)
Chemically Synthesized Oligonucleotides	657	(1)
The Polymerase Chain Reaction (PCR) Amplifies DNAs by Repeated Rounds of DNA Replication in vitro	658	(2)
Nested Sets of DNA Fragments Reveal Nucleotide Sequences	660	(1)
Forensics and the Polymerase Chain Reaction	661	(2)
Shotgun Sequencing a Bacterial Genome	663	(1)
The Shotgun Strategy Permits a Partial Assembly of Large Genome Sequences	664	(1)
Sequenators Are Used for High Throughput Sequencing	665	(1)
The Paired-End Strategy Permits the Assembly of Large Genome Scaffolds	666	(1)
Genome-Wide Analyses	667	(2)
Comparative Genome Analysis	669	(3)
Proteins	672	(9)
Specific Proteins Can Be Purified from Cell Extracts	672	(1)
Purification of a Protein Requires a Specific Assay	673	(1)
Preparation of Cell Extracts Containing Active Proteins	673	(1)
Proteins Can Be Separated from One Another Using Column Chromatography	673	(1)
Affinity Chromatography Can Facilitate More Rapid Protein Purification	674	(1)
Separation of Proteins on Polyacrylamide Gels	675	(1)
Antibodies Visualize Electrophoretically-Separated Proteins	676	(1)
Protein Molecules Can Be Directly Sequenced	676	(1)
Proteomics	677	(2)
Bibliography	679	(2)
Model Organisms	681	(32)
Bacteriophage	682	(5)
Assays of Phage Growth	684	(1)
The Single-Step Growth Curve	685	(1)
Phage Crosses and Complementation Tests	685	(1)
Transduction and Recombinant DNA	686	(1)
Bacteria	687	(6)
Assays of Bacterial Growth	687	(1)
Bacteria Exchange DNA by Sexual Conjugation, Phage-Mediated Transduction, and DNA-Mediated Transformation	688	(1)
Bacterial Plasmids Can Be Used as Cloning Vectors	689	(1)
Transposons Can Be Used to Generate Insertional Mutations and Gene and Operon Fusions	689	(1)
Studies on the Molecular Biology of Bacteria Have Been Enhanced by Recombinant DNA Technology, Whole-Genome Sequencing, and Transcriptional Profiling	690	(1)
Biochemical Analysis Is Especially Powerful in Simple Cells with Well-Developed Tools of Traditional and Molecular Genetics	691	(1)
Bacteria Are Accessible to Cytological Analysis	691	(1)
Phage and Bacteria Told Us Most of the Fundamental Things about the Gene	692	(1)
Baker's Yeast, Saccharomyces cerevisiae	693	(3)
The Existence of Haploid and Diploid Cells Facilitate Genetic Analysis of S. Cerevisiae	693	(1)
Generating Precise Mutations in Yeast Is Easy	694	(1)
S. cerevisiae Has a Small, Well-Characterized Genome	694	(1)
S. cerevisiae Cells Change Shape as They Grow	695	(1)
The Nematode Worm, Caenorhabditis elegans	696	(3)
C. elegans Has a Very Rapid Life Cycle	696	(1)
C. elegans Is Composed of Relatively Few, Well Studied Cell Lineages	697	(1)
The Cell Death Pathway Was Discovered in C. elegans	698	(1)
RNAi Was Discovered in C. elegans	698	(1)
The Fruit Fly, Drosophila melanogaster	699	(6)
Drosophila Has a Rapid Life Cycle	699	(1)
The First Genome Maps Were Produced in Drosophila	700	(2)
Genetic Mosaics Permit the Analysis of Lethal Genes in Adult Flies	702	(1)
The Yeast FLP Recombinase Permits the Efficient Production of Genetic Mosaics	703	(1)
It is Easy to Create Transgenic Fruit Flies that Carry Foreign DNA	703	(2)
The House Mouse, Mus musculus	705	(8)
Mouse Embryonic Development Depends on Stem Cells	706	(1)
It is Easy to Introduce Foreign DNA into the Mouse Embryo	707	(1)
Homologous Recombination Permits the Selective Ablation of Individual Genes	707	(2)
Mice Exhibit Epigenetic Inheritance	709	(2)
Bibliography	711	(2)
Index	713