The motivation for us to produce a treatise on regulation was mainly our convic- tion that it would be fun, and at the same time productive, to approach the subject in a way that differs from that of other treatises. We had ourselves written reviews for various volumes over the years, most of them bringing together all possible facts relevant to a particular operon, virus, or biosynthetic system. And we were not convinced of the value of such reviews for anyone but the expert in the field reviewed. We thought it might be more interesting and more instructive-for both author and reader-to avoid reviewing topics that anyone scientist might work on, but instead to review the various parts of what many different scientists work on. Cutting across the traditional boundaries that have separated the subjects in past volumes on regulation is not an easy thing to do-not because it is difficult to think of what interesting topics should replace the old ones, but because it is difficult to find authors who possess sufficient breadth of knowledge and who are willing to write about areas outside those pursued in their own laboratories. For example, no one scientist works on suppression per se. He may study the structure of suppressor tRNAs in Escherichia coli, he may study phenotypic suppression of various characters in drosophila, he may study polarity in gene expression, and so on.

Contenuti

1 Strategies of Genetic Regulation in Prokaryotes.- 1 Introduction.- 2 The Prokaryotic Chromosome and Its Genes.- 3 Gene Clustering and the Operon Concept.- 4 Regulatory Molecules and the Genes with Which They Interact.- 4.1 The Promoter.- 4.2 The Operator and Initiator Genes.- 4.3 Regulatory Proteins and the Small Molecules That Affect Their Activities.- 5 Induction and Repression.- 5.1 Induction.- 5.2 Repression.- 5.3 The Regulon.- 6 Autogenous Regulation.- 7 Integration of Regulatory Mechanisms.- 7.1 Catabolite Repression.- 7.2 Stringency.- 8 Translational Control.- 9 Conclusion.- References.- 2 Structure of Complex Operons.- 1 Evolution of the Operon Concept.- 2 Types of Complex Operons.- 2.1 Internal Promoters and Multiple Promoters.- 2.2 Antitermination and Antiattenuation.- 2.3 Divergent Transcription.- 2.4 Overlapping Transcription.- 3 Evolution of Complexity.- 4 Methodological Implications for Studies of Genome Organization.- 4.1 Use of the Cis/Trans Test.- 4.2 Cis-Acting Proteins.- References.- 3 Autogenous and Classical Regulation of Gene Expression: A General Theory and Experimental Evidence.- 1 Introduction.- 2 Repressors and Activators.- 2.1 Inducible Catabolic Systems.- 2.2 Repressible Biosynthetic Systems.- 2.3 Inducible Drug Resistance.- 2.4 Inducible Prophages.- 2.5 Other Systems.- 3 Inducible Systems.- 3.1 Criteria for Functional Effectiveness.- 3.2 Autogenous and Classical Regulation.- 3.3 Predictions.- 3.4 Arabinose.- 3.5 Other Activator-Controlled Inducible Catabolic Systems.- 3.6 Histidine Utilization.- 3.7 Other Repressor-Controlled Inducible Catabolic Systems.- 3.8 Inducible Biosynthetic Systems.- 3.9 Inducible Drug Resistance.- 3.10 Inducible Prophage Lambda.- 4 Repressible Systems.- 4.1 Criteria for Functional Effectiveness.- 4.2 Autogenous and Classical Regulation.- 4.3 Predictions.- 4.4 Tryptophan.- 4.5 Arginine.- 4.6 Histidine.- 4.7 Isoleucine-Valine.- 4.8 Repressible Drug Sensitivity.- 5 Autonomous Systems.- 5.1 Functional Implications and Predictions.- 5.2 Regulator of the Arabinose Operon.- 5.3 Regulator of DNA Replication.- 5.4 6-Phosphogluconate Dehydrogenase.- 5.5 T Antigen.- 5.6 Transcription Termination Factor Rho.- 5.7 RNA Polymerase.- 5.8 Histones.- 5.9 Unwinding Protein.- 5.10 Scaffolding Protein.- 6 Discussion.- References.- 4 Regulation of Enzyme Synthesis in the Bacteria: A Comparative and Evolutionary Study.- 1 Introduction.- 2 The Nature of the Evidence.- 2.1 Theories of Regulation of Enzyme Synthesis.- 2.2 Gene Arrangements.- 2.3 The Experimental Approach.- 3 The Molecular Basis of Regulation of Gene Expression.- 3.1 Binding Domains.- 3.2 Origins of Regulatory Genes.- 4 The Biosynthesis of Aromatic Amino Acids.- 4.1 Aromatic Pathway Enzymes and Regulation in Escherichia coli.- 4.2 Aromatic Pathway Enzymes and Regulation in Bacillus.- 4.3 Aromatic Pathway Enzymes and Regulation in Other Genera.- 4.4 Genes and Enzymes of Tryptophan Biosynthesis.- 5 Catabolic Pathways.- 5.1 Induction and Repression.- 5.2 Catabolism of Aromatic Compounds.- 5.3 The ?-Ketoadipate Pathway.- 5.4 Meta Pathway Enzymes.- 5.5 Arrangements of Genes of Aromatic Pathway Enzymes.- 5.6 Plasmids and Regulation.- 6 Nitrogen Metabolism and Regulation.- 6.1 Glutamine Synthetase.- 6.2 Nitrogen Regulation in Fungi.- 7 Experimental Evolution.- 7.1 Growth on Novel Substrates.- 7.2 Amidase.- 7.3 Evolved ?-Galactosidase.- 7.4 Gene Duplications.- 7.5 New Metabolic Pathways.- 8 Discussion.- References.- 5 Importance of Symmetry and Conformational Flexibility in DNA Structure for Understanding Protein-DNA Interactions.- 1 Introduction.- 2 Symmetry in DNA Structure.- 3 Flexibility in DNA Structure—The Kink.- 4 Detailed Models for Drug-DNA Binding.- 4.1 Ethidium.- 4.2 Actinomycin.- 4.3 Irehdiamine.- 5 Nature of DNA Breathing.- 6 Organization of DNA in Chromatin.- 7 Active Form of DNA in Transcription, Replication, and Recombination.- 8 Operator-Repressor Interactions.- 9 Concluding Remarks.- References.- 6 Some Aspects of the Regulation of DNA Replication in Escherichia coli.- 1 Introduction.- 2 DNA Replication in Escherichia coli.- 3 Stoichiometry of DNA Replication.- 4 Regulation Is at the Level of Initiating Chromosome (or Replicon) Replication.- 5 The Replication Complex.- 6 The Destruction of the Replication Complex.- 7 Repair Replication (a Possible Example of Regulative Assembly).- 8 Regulation of the Quality of DNA Replication.- 9 RNA and the Initiation of Replication.- 10 Conclusion.- References.- 7 Genetic Control Signals in DNA.- 1 DNA Control Signals.- 1.1 Introduction.- 1.2 DNA Sequence.- 1.3 Sequence-Specific Protein-DNA Interactions.- 1.4 Genetics of Control Signals.- 1.5 DNA Sequence Analysis.- 1.6 Chemical Probes.- 1.7 General Information in DNA.- 2 Transcription Control Signals.- 2.1 The Transcription Unit.- 2.2 Development versus Maintenance.- 2.3 Control of Transcription.- 3 The Promoter and Its Regulation.- 3.1 The Promoter.- 3.2 Transcription Initiation.- 3.3 The RNA Polymerase.- 3.4 The Basic Promoter.- 3.5 Promoter Function—The Model.- 3.6 Energy-Information Coupling.- 3.7 Binding Energy and Kinetics.- 3.8 Justifying the Model.- 3.9 Promoter Strength.- 3.10 Promoter Activation.- 3.11 Repressors, Operators, and Negative Control.- 3.12 Promoters and Development.- 4 The Terminator and Its Function.- 4.1 Terminators and Rho Factor.- 4.2 Attenuators.- 4.3 Rho-Dependent and Rho-Independent Terminators.- 4.4 Reversing Initiation … Somewhat.- 4.5 The Basic Terminator.- 4.6. Polymerase-Terminator DNA Interactions.- 4.7 RNA Structure and Braking.- 4.8 Terminator DNA Melting.- 4.9 RNA Elimination.- 4.10 Concerted Process.- 4.11 Rho-Dependent Termination.- 4.12 Translation and Transcript Termination.- 4.13 Terminator Strength.- 5 Terminator Regulation.- 5.1 Regulation and Rho Factor.- 5.2 The trp Attenuator.- 5.3 Control by Antitermination.- 6 Concluding Remarks.- 6.1 Transcription Regulatory Mechanisms.- 6.2 Adaptive Response versus Development.- 6.3 A Problem in Genetic Design.- References.- 8 On the Molecular Bases of the Specificity of Interaction of Transcriptional Proteins with Genome DNA.- 1 Introduction.- 2 Molecular Bases of Protein-Nucleic Acid Interactions.- 2.1 Protein Structures and Functional Groups.- 2.2 Nucleic Acid Conformations and Functional Groups.- 3 The Problem of the Other Sites.- 3.1 Informational Aspects of Regulation.- 3.2 Thermodynamic Aspects of Recognition.- 3.3 Methods for Studying Specific and Nonspecific Binding of Proteins to Nucleic Acids and Definitions of Interaction Parameters.- 4 The Lactose Operon of Escherichia coli.- 4.1 lac Repressor-Operator-Inducer-DNA Interactions.- 4.2 Repression of the Lactose Operon as an Integrated Control System.- 4.3 In Vivo Determination of the Thermodynamic Parameters of the lac System.- 4.4 Kinetics of Intracellular Repressor Transport.- 4.5 Other Components of the Lactose Operon.- 5 Extension to Other Transcription Regulatory Systems.- 5.1 Prokaryotic Control Systems.- 5.2 Eukaryotic Control Systems.- References.- 9 Genetic Signals and Nucleotide Sequences in Messenger RNA.- 1 Introduction.- 2 Ribosome Recognition of Initiation Signals.- 2.1 A Bit of History.- 2.2 A Look at Today’s Catalog of Ribosome-Binding Sites.- 2.3 mRNA and rRNA Pair during Initiation.- 2.4 Proteins as Determinants in Initiation.- 2.5 RNA versus Proteins in Species Specificity.- 2.6 mRNA Structure and Initiation.- 2.7 Translational Control at the Molecular Level.- 2.8 The Why and Wherefore of Translational Restarts.- 2.9 Mutations in Ribosome-Binding Sites.- 2.10 Perspectives and Problems.- 3 Sequences Directing Elongation of Polypeptide Chains.- 3.1 Selective Codon Usage in Bacteriophage Messengers.- 3.2 Overlapping Genes and Signals in Messenger RNA.- 4 RNA � RNA Interactions in Ribosome Function.- 5 Are Eukaryotic Messengers Different?.- References.- 10 The Role of tRNA in Regulation.- 1 Introduction.- 1.1 Biosynthesis of tRNA.- 1.2 tRNA in Protein Synthesis.- 2 tRNA as a Regulatory Molecule.- 2.1 Stringent Control.- 2.2 Operon-Specific Control.- 3 tRNA as a Target for Regulation.- 3.1 tRNA-Dependent Modulation of Translation: An Evolutionary Equilibrium.- 3.2 tRNA-Dependent Modulation of Translation: A Developmental Regulation.- 4 tRNA Has Other Functions.- 5 Concluding Remarks.- References.- 11 Suppression.- 1 Introduction.- 2 A Short Synopsis of Suppression.- 2.1 How It Started.- 2.2 The Problem of Nomenclature.- 2.3 Nonsense Suppression.- 2.4 Missense Suppression.- 2.5 Frameshift Suppression.- 2.6 Ribosomal Suppression.- 2.7 Polarity Suppression.- 3 Some Topics in Molecular Biology Influenced by Analysis of Genetic Suppression.- 3.1 Phasing of Messenger RNA.- 3.2 UAG, UAA, and UGA in Polypeptide Chain Termination.- 3.3 Effect of tRNA Modification on Codon Specificity.- 3.4 How Specific Is Codon � Anticodon Interaction?.- 3.5 Other Errors in Translation.- 3.6 Polarity and the Coupling of Transcription to Translation in Bacteria.- 3.7 Genetics of tRNA.- 3.8 Biosynthesis of tRNAs.- 3.9 tRNA Structure-Function Relationships: Mischarging Suppressor tRNAs.- 4 Nonsense Mutations in the Escherichia coli lacI Gene.- 4.1 Suppression of Nonsense Mutations Generates Altered lac Repressor Molecules.- 5 Current Developments in Eukaryotic Suppression.- 5.1 tRNA-Mediated Suppression in Yeast.- 5.2 The Search for Nonsense Mutations and Their Suppressors in Drosophila and Mammalian Cells.- 6 Outlook.- References.- 12 Regulation of the Protein-Synthesizing Machinery—Ribosomes, tRNA, Factors, and So On.- 1 Introduction.- 2 The Concepts and Elements.- 2.1 Characteristics of Control at the Operon Level.- 2.2 Transcription and the Regulation of the Protein-Synthesizing System.- 2.3 Relations between the Major Synthetic Activities.- 2.4 Parameters Characterizing Steady States of Growth.- 3. Patterns and Frequencies of Transcription.- 3.1 Protein Synthesis at Medium and High Growth Rates.- 3.2 Protein Synthesis at Low Growth Rates.- 3.3 The Amino Acids-Substrates and Effectors.- 3.4 Transcription and Translation Frequencies.- 3.5 Synopsis.- 4 The Role of ppGpp in Regulation of the Protein-Synthesizing System.- 4.1 ppGpp Concentrations.- 4.2 The Relaxed Syndrome.- 4.3 Ribosome and Protein Synthesis during Shift-Down Transients.- 4.4 The Low Efficiency of Ribosomes at Low Growth Rates.- 4.5 Synopsis.- 5 Ribosome Synthesis during the Cell Cycle.- 6 Afterthoughts.- References.

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