Index

Acetamide, arrangement of genes for, 144 AcinelObacter calcoaceticus

f3-ketoadipate pathway in, 134 tryptophan biosynthesis in, 131-132

Acinetobacter species, mandelate enzymes in, 137-138

Acridine orange chemical structure of, 177 and intercalation with DNA, 176

Actinomine, and ethidium, 181 Actinomycin

chemical structure of, 177 and intercalation with DNA, 176 mode of action, 181-182

Actinomycin-DNA binding model, 178-182 and guanine specificity, 187

Activator mechanisms for cysteine biosynthesis, 63 for isoleucine-valine biosynthesis, 63

Activators, 5, 59-66 autogenously regulated, 67 regulators as, 58 unregulated, 67

Active initiator region, 377-378 Aerobacter aerogenes

and gene duplication, 153-154 growth in L-fucose, 155

Aerobic degradation of aromatic compounds, 134 Aerobic growth, energy consumed in steady states

of, 505 Aggregation, in aromatic pathway enzymes, 124,

127 Alarmones, 16 Amidase, 150-/52

growth on novel substrate, 150-151 mutants, 150-/5/ regulation of, 150-/51 substrate specificities of, 157

Amino acid biosynthesis pleiotropic controls of, 418 regulatory systems of, 159-160

543

Amino acids biosynthesis regulation, 63-64 endogenous biosynthesis of, 63 and macromolecular syntheses, 504-507 pool levels, 506

Amino acids, aromatic, biosynthesis of, 123-132 Aminoacridine, chemical structure of, 177 9-Aminoacridine, and intercalation with DNA, 176 Aminoacyl-tRNA ligases, stringent control of, 406-

407 Aminoacyl-tRNA synthetase, specificity of, 464 Ammonia assimilation, enzymes for, 146 Amphibolic operons, repression of, 505 Amphibolism, 499 Anthranilate synthetase

as activator, 81 role in trp operon regulation, 81

Antibiotics, and drug-resistant microorganisms, 64-65

Anticodon modification, 449-450 Anticodon specificity, relaxed, 453 Antiinducers, 312 Antitermination, 26

control by, 264-267 and lambda development, 266-267 lambda N gene and, 264-265 mechanisms of, 41, 265-266 in phage lambda, 32-38 recognition sites in, 40-41 and rho-dependent termination, 264 specificity of, 39

Aporepressor, 5, 8 in cumulative repression, 10 in multivalent repression, 10

Arabinose, in E. coli, classical control in, 69-70 Arabinose operon, regulator of, 89 Arginine, absorption, 63 Arginine biosynthesis, regulation of, 116

arrangement of genes for, 144 autogenous regulation in, 82 in E. coli, 82

544

INDEX

Arginine biosynthesis, regulation of (cant.) regulation of, 82 structural genes of, 82

Aromatic acid biosynthesis in B. subtilis, 127-129 channel-shuttle model, control system in, 129-

130 characteristics of, 124 in E. coli, 124-127 feedback inhibition in, 124, 126, 127-128, 129 gene clustering in, 128-129 isoenzymes in, 124-125 pathways for, 125 regulation of, 127-128

Aromatic compounds, catabolism of, 133-134 Aromatic pathway enzymes

gene arrangement in, 143-144 and plastids, 144-145

Aspergillus nidulans enzyme regulation studies in, 148-149 nitrate reductase system in, 73-74 regulation of amidases in, 148

Attenuation, controlled, in E. coli, 39-40 Attenuator, 9

definition, 251 frequency of termination at, 39 and RNA polymerase, 415 in trp operon, 39-40 and tryptophan, 39

A . U base pairs, stereochemistry of, 290 Autogenous regulation, 11-12, 58

in arginine system, 82 definitions, 96-97, 113 development or: 113 functional, 97 and gene transcription, 147 and histidine utilization (hut) system, 72, 83 and inducible catabolic systems, 68

Autonomous systems, 16, 88-96 arabinose operon regulator, 89 definition, 98 DNA replication regulator, 89-90 histones, 93-94 6-phosphogluconate dehydrogenase, 90 predictions, 88 scaffolding protein, 96 T antigen, 90-91 termination factor Rho, 91-93 unwinding protein, 94-96

Bacillus licheniformis penicillin resistance in, 65 penicillinase system in, 75-76

Bacillus sp., catabolic repression in, 152 Bacillus stearothermophilus, ribosomes of, 361-363

phage sites bound by, 362 Bacillus subtilis

aromatic pathway enzymes in, 127-129 inducer in, 113 sigma factors in, 248-249 tryptophan biosynthesis in, 131-132 vegetative-to-sporulation change in, 249

Bacteria characteristics of, 109 genetic regulation in, 19 lysogenic, 23

Bacterial chromosome replication and DNA synthesis, 204-205 sequential process of, 204

Bacteriophage lambda, 19 induction control of, 66

Bacteriophage messengers, selective codon usage in <l>XI74,382-383 MS2, 380-382

Bacteriophage MS2 RNA nucleotide sequence of, 364 predicted secondary structure of, 364

Bacteriophage R 17, 15 Bacteriophage RI7 RNA, segment protected by

coat protein, 365 Bacteriophage T 4, 15

nonsense suppressing derivatives of, 463 Bacteriophage T7, multiple promoters in, 31-32 Base composition, 298-299 Base sequences

assumptions chemical randomness, 300 variance of probabilities, 299-300

probability of occurrence, 295-299 base composition, 298-299 purine or pyrimidine loci, 298

!3-kinked DNA conversion to exclusion-intercalative structure,

190-191 recognition by E. coli RNA polymerase, 191

!3-kinked B DNA structure, computer illustration of, 183

Bifunctional complementary intermolecular inter­actions, specificity of, 282

Binding antiinducer, 312 bonds, 223-224 dependence on ionic strength, 315 energy, 223-224 inducer, 312 intersubunit, 310 protein-DNA, 222-223 reversible, 224-225

Binding free energies. distribution of, 304-305 Binding parameters. 307, 308 Binding sites

inducer, 120 operator, 120

Biosynthesis nucleic acid, 45 of tRNA, 402-403

Biosynthetic enzymes control proteins of, 492 genes for, 492

Biosynthetic operations, repression of, 505 Biosynthetic pathways

regulators of, 63 repressible, 62

Biosynthetic systems inducible, 74-75 repressible, 63, 77-88

Biotin cluster, in E. coli, 41-45 common control region in, 43 mutations in, 43 transcription, 42-43

Bombyx mori, protein biosynthesis in, 422-423

Bonding covalent, 229 hydrogen, 283 hydrophobic, 283

Braking catalytic, 258 elimination of, 256 and RNA structure, 255-257

cAMP-CAP activation, 243-244 CAP, see CAP-cAMP system, CAP protein; cata­

bolic gene activator protein; cyclic AMP receptor protein

CAP-cAMP system, 13,243-244, 340-341 model for, 341

CAP protein (Escherichia coli) binding sequence, 243-244 as pleiotropic activator, 13-14, 243 and sigma factor, 243

Carbohydrates, metabolism of "unnatural," 155 Carbon repression, as enzyme system control, 148-

149 Catabolic enzymes

control proteins of, 492 genes for, 492 regulation of, 13-14, 133

Catabolic gene activator protein (CAP), 13, 112, 243-244, 340-341

Catabolic pathway enzymes evolution of, 160 regulatory proteins of, 160-161

Catabolic pathways for aromatic compounds, 133-134 aromatic gene arrangement in, 143-144 induction, 133 of ,B-ketoadipate, 134-141 meta enzymes, 141-143 plasmid regulation, 144-145 repression, 133 role of plasmids in, 144-145

Catabolic systems, inducible, 60-63 arabinose, 61 effectiveness criteria for, 67-68 galactose, 60 glycerol, 60 histidine utilization, 60 lactose, 60 regulation of, 67 rhamnose, 61

Catabolite repression, 7, 489 advantages of, 13-14 in E. coli, 112 operons in, 13

Catabolite repressor protein (CRP), 13, 243-244, 340-341

Catechol pathways enzymes of, 140-141 regulatory genes of, 138-140

Cell cycle, ribosome synthesis during, 535-537 Cell growth, arrest, and tRNA, 409 Cell reactions

regulatory, 404 structural, 404

Channel-shuttle model, for aromatic acid biosyn­thesis control, 129-130

Chemical probes, for protein-DNA contact identi­fication, 229

Chloramphenicol induced resistance to, 65, 75 and repair replication, 210 repressor protein control of, 65 resistance to, 76 and stringent response, 408

Chromatin, organization of DNA in, 185-190 Chromosome, prokaryotic

genes of, 2-3 molecular structure, 2

Chromosomes, gene arrangement on, 122 Cis-acting proteins, 50-51 Cis / trans test, 50 Cistron, 4 Cloverleaf structure, of tRNA, 402 Clustering

adaptive value of, 47 of genes, see Operon concept

Clustering, supraoperonic, of catabolic genes, 144 Coat protein synthesis, repression of, 369-370 Codon' anticodon interaction

and hydrogen bonding, 453-454 specificity of, 449-450, 451-454 strength of, 450

Codon-dependent translational selectivity, tRN A, 421

Codon recognition studies, 444 Codon specificity, effect of tRNA modification on,

449-451 Codon table, 453 Conformational motility, and protein-nucleic acid

interaction, 291 Constitutive operon, as probe for repression, 510 Control, stringent, 14, 526 Control characteristics, at operon level, 488-489 Control sequences, and protein binding, 221-222 Control signals

effect of mutations on, 227-228 genetics of, 227-228 transcription, 2-3, 230-231

Control systems eukaryotic, 342-343 prokaryotic, 1-17,341-342

Core proteins, active synthesis control of,517-518 Corepressor, 5, 8-9 Corey-Pauling-Koltun (CPK) molecular models,

190 Coupling

energy-information, 235-236 mechanisms, 509 transcription-translation, 508-510

CPK, see Corey-Pauling-Koltun molecular models ero protein

negative regulation by, 38 in phage lambda, 37-38

CRP, see Cyclic AMP receptor protein Cumulative repression, 9-10 Cyclic AMP receptor protein (CRP), 112

D-arabinose, novel pathways for use of, 156 D-arabitol, novel pathway for catabolism of, 159 D-serine,6

activator control of, 70 deaminase system in, 70

545

INDEX

546

INDEX

Daunomycin, and intercalation with DNA, 176 Deletion, in gene clusters, 42 Destabilization

artificial, 256 complex, 258 hybrid, 258

Dipolar alignment, and protein-nucleic acid sta­bility, 284

DNA A-form geometry, 292 B-form geometry, 292 circular, 2 conformational structure fluctuations, 184 control signals in, 219-269 control systems in, 220 Corey-Pauling-Koltun model, 190 functions, 2, 3 nonoperator, 317-319 replication, 220 sense strand, 2 sequence, 221 "silent," 220 supercoiled, 239 unwinding of, 190

DNA base pairs, functional groups, distances and angles, 288

DNA breathing and drug intercalation, 184-185 and formaldehyde, 184 nature of, 184-185 structural predictions based on, 191

DNA chain elongation, mechanics of, 202-203 DNA denaturation, structural predictions based

on, 191 DNA double helix, antiparallel nature of, 202 DNA melting, 185 DNA overwinding, polymerase-induced, 239 DNA polymerase-genome interaction, binding

parameters characterizing, 340 DNA-protein recognition specificity, elements of,

280 DNA replication

conditional forms of, 206 in E. coli, 201-203

characteristics of, 205-206 genes essential for, 202 and mutants, 208

delayed stop, 204 immediate stop, 202 initiation, 202

nonterminating, 210 quality regulation of, 211 recycling, 210 regulator of, 89 and relative gene numbers, 494 restrictions on, 203 stoichiometry of, 203-204, 212 and temperature-sensitive mutants, 202

DNA sequence analysis of, 228-229 general features of, 229-230 protein discrimination of, 226

DNA structure, 171-196 axes in, 172 bending of, 173-174 flexibility in, 173-176

DNA structure (cont.) flexible hinge in, 184 H-bond contacts, 225-226 ionic contacts, 225 kinked, 173-174 symmetry in, 172-173

DNA synthesis, temperature sensitive, 205 DNA thermal denaturation, and sequence-specific

drugs, 191 Drosophila

frameshift mutations in, 473 tRNA suppressors in, 473

Drosophila development, tRNA-dependent trans­lation modulation in, 423

Drug-DNA binding, models for, 176-184 Drug-nucleic acid crystalline complexes, forma­

tion of, 176 Drug resistance

chloramphenicol, 75 erythromycin, 75 inducible, 62, 64-65, 75 penicillin, 75 and plasmids, 144-145 role of transposons in, 144 tetracycline, 75

Drug sensitivity effectiveness criteria for, 86-87 to erythromycin, 87 repressible, 86 to tetracycline, 87

Duplication, internal, within genes, 123 Dyad axes, DNA

computer illustrations of, 172 flexibility of, 173

Effector-induced repression, 245 Effectors

and concentration-dependent equilibria, 222 and macromolecular syntheses, 504-507

Endonucleases, and tRNA maturation, 403 Energetics, of reversible binding, 224-225 Enzyme(s)

aromatic pathway, 124-129, 143-144 as aggregates, 124, 127 location of genes for, 124, 128 multiple functions of, 124, 126-127 regulatory genes for, 124, 125-126

bifunctional, 125 biosynthetic, 492 catabolic, 492 fungal, 148-149 mandelate, 135-138 meta pathway, 141-143 multifunctional, and fused structural genes, 123 restriction, 300

Enzyme activity, evolutionary theories of, 110 Enzyme evolution, and gene duplication, 122 Enzyme induction

competitive repression of, 151 mass action theory of, 112

Enzyme synthesis common regulation of, 119 experimental studies, 117-119

ammonia assimilation, 118 growth studies, 118-119 metabolic pathway regulation, 118

Enzyme synthesis (cont.) regulation, in bacteria, 109-162 regulation theories, 111-114

Enzyme system controls, 148 Epimerase, and cAMP, 40-41 Error-prone repair system (SOS)

spontaneous expression of, 210 and ultraviolet light, 210

Erythromycin induced resistance to, 65, 75 repressed sensitivity to, 87 repressor protein control of, 65

Escherichia coli, 6, 7, 8, 13, 33, 40, 48, 49, 63 arabinose system in, 69 aromatic pathway enzymes, 124-127 attenuatAr in, 39-40 biotin cluster of, 41-45 chromosome duplications, 114-115 chromosome map, 124 D-arabitol metabolism in, 154 evolution of regulator in, 116 evolutionary increase In genetic potential of, 115 gene clustering in, 115-116 gene duplication in, 115 gene-enzyme systems in, 114 gene transposition, 115 genetic loci on chromosomes of, 203-204 genetic mapping for, 114 genome of, 459 "glucose effect" in, 112 and glucose preference, 247 glucose uptake inhibition, 527-528 glutamine synthetase in, 146 isoleucine-valine biosynthesis in, 84-85 lac control, 246-247 lac operon of, 19 lac repressor and operator, 246, 247 lactose operon of, 308-341 minicell mutant of, 331 missense suppression in, 450 nonsense mutations in, 466-468

schematic diagram of, 467 potential binding sites in, 293-295 protein synthesis arrest, and stringent response,

408-409 protein synthesis rate measurements, 495 pseudouridylate synthesis in, 411 regulation of DNA replication in,.201-213 ribitol metabolism in, 154 RNA polymerase, 232

recognition of J3-kinked DNA structure, 191 RNA polymerase sigma factor, 248 tetracycline resistance in, 65, 75 trp operon of, 22, 32 tryptophan biosynthesis in, 130-131

Escherichia coli cell, wild type, parameters of, 321-323

Escherichia coli replication, characteristics of, 205-206

effect of growth conditions on, 206 Escherichia coli ribosomes, initiation sequences

recognized by, 354-355 Escherichia coli RNA polymerase, 337 Escherichia coli tRNA genes, map locations of, 460 Ethidium

and actinomine competition, 181

Ethidium (cont.) allosteric transition induced by, 184 binding sites for, 190 chemical structure of, 177 and intercalation with DNA, 176 sequence-dependent pyrimidine in, 181

Ethidium bromide binding effects of salt concentrations on, 184 fluorescence Scatchard plots of, 182

Ethidium-DNA binding model, 180 angular unwinding in, 179 computer illustration of, 179 construction of, 178 steps in assembly of, 177

Ethyl nitrosourea, as organic chemical probe, 194 Eukaryote(s)

multiple replicons in, 205 quiescent state induction, 408 stringent control in, 408 suppression in, 434

Eukaryote genes, tRNA controlled expression of, 417-419

Eukaryotic cell, nuclear membrane of, 387 Eukaryotic messengers, 387-389

covalent modifications in, 387-388 genetic signals in, 388 initiator region recognition in, 388-389 monocistronic, 387

Eukaryotic suppression nonsense mutations and suppression

in Drosophila, 472-473 in mammalian cells, 472-474

tRNA-mediated suppression in, 469-472 Evolution

of catabolic pathways for D-arabitol, 154 for ribitol, 154

of enzymes, 161 due to mutational divergence, 110

experimental systems for study of, 149-159 novel substrates, 149-150

induction mechanisms in bacteria, 135 laboratory studies of, III lambda, 47-48 of operon complexity, 47-50 of regulation in tryptophan biosynthesis, 132 of regulator molecule, 116 of regulator proteins, 161 of regulatory genes, 138-140 of viruses, 47

Excision action of, 29 catalytic requirements of, 28

Excisionase, 28 Exonuclease, 33

gene, induction of, 33 synthesis, 33-34

Extrachromosomal elements, see Plastids Extrachromosomal genetic units, and suppression

of delayed stop mutants, 205

Feedback inhibition in aromatic acid biosynthesis, 124, 126, 127-128,

129 for enzyme activity regulation, 114

Feedback mechanism, in lac operon, 309

547

INDEX

548

INDEX

Frameshift mutations, suppressors in S. cerevisiae, 471

Frameshift suppressors generation of, 441 in Salmonella typhimurium, 437

Fungi biosynthetic pathways of, 64 nitrogen regulation in, 148-149

Fusions, genetic, 35

G-I restriction point, in cell cycle, 409 f3 -Galactosidase

evolved, 152-153 operon, regulator mutants of, 152 and lac repressors, 19-20

G· C base pairs bifunctional interaction, 291 stereochemistry of, 290

G· C sequence contacts, 254-255 Gene(s)

alteration in expression of, 16 ora C, 69-70 autogenous regulation of, 95 bio,34 biosynthetic enzyme, 492 C/, control of, 23-24 C/I,34 clustering, 3-4 clusters, 41-45 core, 491 era, 34 cyclic AMP, differential effect of, 41 duplication, 115 expression of, regulation, 3 fusion, 122 gal, 34-35

induction of, 38 polarity of, 37

initiator, 4-5, 6 int, 23-24, 27-28 lac, 19-21 operator, 4-5 operator-distal, 80 overlapping, 383-384 P2 int transcription, 31 phosphoribosyltransferase, 49 polarity in, 34-36 positive activator, 5 prophage, 23 regulation of scattered, II regulatory, 7-10 relA, and relaxed control, 14 rex, 23-24 rho, 37 r-protein, 495 silent, 115 stable RNA, 491-492 structural, 2, 7-10

constituitive, 3 32, and unwinding protein, 94-95 transcribed from promoters, 23-30 transcription of, 15-16 in transcription unit, 230 translocation, 115 transportation, 115 tryptophan biosynthetic, 49

Gene(s) (cant.) viral, 23 xis, 28

Gene amplification, and drug resistance, 65 Gene duplication

advantages of, 153 compared to catabolic plasmids, 154 and evolutionary divergence of proteins, 121 internal, 110 objections to, 161 as regulatory mechanism, 122

Gene expression controlled by activator, 61 controlled by repressor, 60 and drug resistance, 65 lac, 246-247 molecular basis

binding domains, 119-121 regulatory gene origins, 121-123

negative control over, 5, 365 positive control over, 5-6 regulation of, 57-100 and somatic cell hybridization, 66

Gene fusion experimental production of, 123 and multifunctional enzymes, 123

Gene transcription, tRNA-dependent control of, 418

Genetic control signals in DNA, 3, 219-269 promoter regulation, 4, 231-250 terminator, 250-267 transcription, 230-231

Genetic regulation objectives of, 219 by operon, 3-4 in prokaryotes, 1-17 by regulon, II and transcription, 219-220

Genome function, transcriptional control of, 279-281

Genome organization, methodological implications for, 50

Glucose catabolism, location of genes governing, 115

"Glucose effect," see Catabolite repression Glutamate synthetase

autogenous controls of, 147 effect of adenylylation on, 147 and immunological cross-reactions, 148

Glutamine as amino acid precursor, 146 regulatory mechanisms for, 146-147

Growth rates effect on protein synthesis, 503 extreme, induction lags at, 502 low

energetics of, 503-504 and passive control, 506 polypeptide chain growth at, 501-503 protein synthesis at, 500-504

of polypeptide chains, 493 and protein synthesis, 469-500 of RNA chains, 493

Guanine specificity in actinomycin-DNA binding, 178, 181 and recognition of actinomycin, 178

Guanosine pentaphosphate, role in stringency mechanism, 14

Guanosine tetra phosphate, see ppGpp

Hairpin structure, RNA, 253 Helical screw axis dislocation, 187-188 his T mutants

and charged/uncharged tRNA ratios, 410, 412 and histidine operon depression studies, 412 and ppGpp biosynthesis, 412 and regulation, 411

Histidine absorption, 64 biosynthesis in Salmonella typhimurium, 83 deprivation, 415 feedback inhibition by, 414 as nitrogen source, 412

Histidine operon, 4 aporepressor for, 83 arrangement of genes for, 144 composition of, 410 depression of, 410 depression studies, 412 hisG regulation of, 414 mutants affecting, 410-411 operon-specific regulation, 415 and ppGpp-dependent transcription, 414-415 regulatory system for, 114 and tRNA concentration, 412-413 tRNAHis regulation of, 410-425

Histidine utilization (hut) system, 71 and auto~enous regulation, 72 degradation enzymes of, 71

Histones binding regions for, 93-94 definition, 93 effect of chromosomal proteins on transcription

in, 93-94 and eukaryotic chromosome, 28211 migration of, 93-94 role of, 93

Homobiotin, repressive effect of, 45 hut, repressor of, 71 Hydrogen bonding, 453

blocking of, 226-227 and coding specificity, 451-452 and codon· anticodon specificity, 453-454 in DNA, 225-226 interbase, 287n in mRNA· rRNA complex, 357 and protein-nucleic acid specificity, 283 spatial coupling with ionic bonds, 226

Hydrophobic bonding, and protein-nucleic acid interaction, 283

Immediate stop mutants and chain elongation, 202 functions of, 202

Inducer, 5 and PSS, 489

Inducer binding and conformational changes caused by, 312-313 effect of, 318-319

Inducible systems, 66-77 arabinose, 68-70

Inducible systems (cont.) D-serine, 70 drug resistance, 75-76 functional effectiveness of, 67-68 histidine utilization, 71-72 isoleucine-valine, 74 lactose, 73 maltose, 70-71 nitrate, 73-74 predictions, 68-69 prophase lambda, 76-77 regulation of, 6-8, 68 tryptoRhan, 74-75

Induction, 6-8 in E. coli, 6 an enzyme system control, 148-149 molecular mechanisms for, 6-8, 66 negative control of, 7 positive control of, 7-8 of prophages, 65-66 spontaneous, 66

Induction mechanisms, evolution of, in bacteria, I35

Inhibition, feedback, 12 Initiation

antibiotic inhibitors of, 353 bidirectional, 45 mRNA· rRNA base pairing during, 353-358 in promoter utilization, 235 protein determinants in, 358-361 reversal of, 251-252

Initiation factor function of, 359-360 requirements for, 358-359

Initiation frequencies, 507-508 Initiation mutants, functions of, 202 Initiation signals, ribosome recognition of, 350 Initiator, 5 Insertion, 27-28

catalytic requirements of, 28 prophage, 29-30 reversal of, 28

Integrase abnormal,31 control,29 lambda, 27-30 in mUltiple promoter systems, 32 P2,30-31 production kinetics, 28 role in viTal cycle, 27-28 specificity, 48 synthesis, 38 transcription rate, 31

Integrase system, dual promoters in, 47 Integrative suppression

by episomes, 205 by plasmids, 205

Intercalative drugs, classes of, 174-176 Intracellular repressor transport

intradomain transfer mechanism, 336 kinetics of, 332-336 sliding mechanism for, 333-335

Ionic bonds demonstration of, 224 in DNA molecule, 225 in protein-DNA interactions, 223-224

549

INDEX

550

INDEX

Irehdiamine-DNA binding model, 180 mimicking of intracalative drug binding, 182

Isoenzymes in aromatic acid biosynthesis, 124-125 origin of, 160 properties of, 160

Isoleucine-valine activator for, 74 biosynthesis in E. coli, 84-85

Isoleucine-valine operon hyperrepressed, 416 tRNA regulation of, 415-416

lacob-Monod operon model, 6, 20--21

K-kinked B DNA, computer illustration of, 186 ,B-Ketoadipate pathway, outline of convergent

catabolic pathways, 134 Kinetic studies, comparative on promoters, 240 Kinking

conversion of, 175 in DNA, 173-174 origin of, 184-185 as spontaneous process, 176

Klebsiella aerogenes, 86n, 118 glutamine synthetase in, 146 inducer in, I I3 mutations in, 155-156 and nitrogen limitation, 147 ribitol dehydrogenase of, 158 ribitol gene linkage in, 154 use of L -fucose pathway enzymes in, 155

L-arabinose metabolism, enzymes of, 112 L-I,2-propanediol

mutants, 158 novel pathway for use of, 157

lac enzymes, concentration maintenance, 309 lacI mRNA, sequences of, 374 lac operator, free in E. coli cell, 323-328

and additional strong repressor-binding sites, 325

basal level of, 323-324 and increased cellular repressor, 325 and inducer-binding effects, 326-327, 33 I and K RW / KRO' K",,/ KRD ratios, 327-328 and operator constitutive mutations, 325-326 and partially saturated inducer-repressor com-

plexes, 329-330 lac operator region, techniques for study of,

192-193 lac repressor

binding thermodynamics of, 320 characteristics of, 192 functional binding domains, 31 I inducer-binding domain in, 310 interactions

with inducer, 311-313 with nonoperator DNA, 317-319 with operator, 313-317

nonspecific binding of, 332 salt dependence of, 315 schematic representation of, 321 subunits of, 309-310

lac repressor tetramers, distribution of, 33 I

lac system regulation of, 6-7, 73 thermodynamic parameter determination of,

330--332 Lactose metabolism, enzymes of, 112 Lactose operon, 308

components of, 336-341 effect of non operator DNA on, 319 feedback mechanism in, 309 genome control system of, 309 repression of, 3 I 9-330 and RNA polymerase, 336 schematic representation of, 310

A, evolution of, 47-48 A development, and antitermination, 266-267 Lambda integrase, 27-30 A N protein

and breaking, 265 function, 264 and terminator regulation, 264-265

Lambda repressor and operators, 247-248 Lambda repressor synthesis, 23-27 Leucine operon

hyperrepressed, 416 tRNA regulation of, 415-416

Ligase sensitivity to stringent control, 406-407 Lysine, arrangement of genes for, 144 Lysogen(s)

double, 31 lambda, 70 P2

depression of, 30 superinfection of, 31

repressed, 28-29 Lysogenization, sequence of events during, 26-27 Lysogeny

autonomous regulator during, 90 establishment of, 24-25 key events in, 27 maintenance of, 24 and PRM, 25

Lytic cycle, control of genes in, 33

Maltose activator for, 70--7 I regulation of, 71

Mammalian systems, nonsense mutations in, 473-474

Mandelate enzymes in Acinetobacter species, 137-138 in Pseudomonas species, 135-137

Melting promoter rate of, 24 I in promoter utilization, 234-235, 238 sequence-specificity of, 239

Messenger RNA, see mRNA Meta pathway enzymes

characteristics, 141- I 42 reactions of, 142- I 43 regulation of, 143 pathway outline, 141

Metabolic pathways, development of new, 154-159

Metabolic regulation, 407 Methylenomycin, synthesis by Streptomyces coeli­

color, 117

Micrococcal nuclease, and intercalative geometry, 189

Microorganisms, drug-resistant, natural selection of,64

Missense suppression, 437 Modulation hypothesis, 419-424 mRNA

core, transcriptional cross-section of, 499-500 genetic signals in, 349-389 half-life, 494 noncore, transcriptional cross-section of, 499-

500 nucleotide sequences in, 349-389 overlapping genes in, 383-384 phasing of, 439-441 predicted secondary structure, 373 signals in, 383-384 size distribution of, 507-508 stability of, evolution of, 494 termination signals in, 445-447

mRNA chain elongation of, 338 initiation of, 338 termination of, 338

mRNA'rRNA complex demonstration of, 356 questions concerning, 357-358 structure of, 356-357

mRNA structure and initiation, 363-367 secondary, 363-366 tertiary, 363-366

mRNA synthesis nucleotide sequences in, 192 and ppGpp, 530

mRNA/total RNA ratio, measurements, 494 MS2 bacteriophage, codons used in, 381 MS2 phage genome, nucleotide sequence of, 363 Multivalent repression, 9-10 Mutagenesis, in vitro, 229 Mutants

affecting tRNA mutation, 403 ambivalent, 435 "computer-generated," 328 with defective inducer-binding region, 120 with defective operator-binding site, 120 delayed-stop, 204 feedback inhibition-resistant, 114 hisO,41O hisR,411 hisS, 410 hisT, 411, 412 hisU, 411 hisW, 411 immediate stop, 202, 204 initiator, 202 minicell, 331

production of, 332 operator constitutive, 315-316 propanediol, 157-158 rII, 435 superrepressed, 120 temperature-sensitive, 202, 204 TRA-3,409

Mutational divergence, 110

Mutations cis-dominant, 227, 231-232 cis-specific regulatory, 44 compensatory, 228 deletion, 36 dominant extragenic, 439-440 in E. coli biotin cluster, 43-44 genetic mapping for, 228 hisR1223,413 hisR1883,413-414 nonsense, 373-374 operator-constitutive, 73, 193 pleiotropic, 232 polar, 35 promoter, 232 regulatory, 50 ribosomal, 456-457 in ribosome-binding sites, 375-377 secondary extragenic suppressor, 436, 437 suppressor type, 435 types, 26

Mutations, secondary, effect of, 433

N protein antiterminating activity of, 36-37 effect on transcription, 34, 38 function of, 35, 38-39 mechanism of action, 34-36 synthesis, 33-34

Natural selection, and operon complexity, 47 Negative control systems, with repressor molecule,

112 Neurospora, tryptophan biosynthesis in, 131 Neurospora crassa, enzyme regulation studies in,

148-149 Nitrate reductase

regulation of, 73-74 as repressor, 148-149

Nitrogen metabolism, regulation of in fungi, 148-149 glutamine synthetase, 145-148

Nitrogen repression, as enzyme system control, 148-149

Noncoordinacy, 15 Noncore proteins, 516-517 Noninitiator, as director of initiation, 375-376 Nonpromoter sequences, on negatively supercoiled

DNA,239 Nonsense mutations

leakiness of, 445 polar effects on gene expression, 457-459 and polypeptide chain termination, 445 suppression of, 468-469

Nonsense suppression generation of, 437 molecular basis for, 433 and nonsense codons, 436 and secondary extragenic mutations, 436 temperature-sensitive, 461 tRNA mediation of, 436 in yeast, 469-472

Nonspecific binding, possible roles of, 305-306 Nonterminating replication, and SOS repair induc­

tion, 210 Nucleic acid

bases, 286-289

551

INDEX

552

INDEX

Nucleic acid (cont.) biosynthesis, 45 conformation, 289-291

Nucleic acid functional groups bases, 286-289 polynucleotide backbones, 284-286

Nucleosomes, solenoidal organization of, 187 Nucleotide backbone unit, 284-286 Nucleotide-binding dehydrogenases, evolution of,

120

One-operon hypothesis and cis-specific proteins, 51 in E. coli biotin cluster, 43-45

Operator, 5, 8, 40 Operator-repressor interactions, 192-195 Operon(s)

activator-controlled, 59 amphibolic, 505 arabinose, 7 biotin, 42-45 biotin-repressible, 42 catabolic, 13-14

induction of, 13 complex types, 21-46

evaluation of, 46 complexity, 20-21

evolution of, 46-50 consequences of beheading, 22 control, 46, 488-489 definition, 3 E. coli, 49 gal, 35, 40-41

rho-dependent attenuator in, 37 his,40

corepressor of, 83 evolution of regulatory theories, 113-114

hur,72 i1v,84-86 inducible, 57, 59-60 interaction, 20 with internal promoters, 121-122 Jacob-~onod,20-2I, 57 lac, 6, 19-21, 112 lambda, 34 linkage, 20 penicillinase, 76 prokaryote, 280 promoter site on, 4 regulation, 20, 46 repressor-controlled, 59 split, 31 sugar, 280 transcription of, 4-5, 46 trp, 21-23, 34-35, 38, 49

attenuator, 80 controlled attenuation in, 39-40 gene duplication in, 126 regulations of, 80 rho-dependent termination of, 35 translocation in, 126

Operon concept, 3-4 and cis-specific proteins, 51 evolution of 19-21

Operon-specific control, 280, 410-419 Operon-specific regulation, and histidine, 415

Organic degradation, mixed microorganisms in, 160

P2 integrase, 30-31 Palindromic sC9,uences, base pair, 293 Pancreatic DNase, and chromatin kink recogni-

tion, 189 Penicillin

induced resistance to, 65, 75 repressor protein control of, 65

Penicillinase, and induced resistance, 75-76 Penicillinase system

in B. licheniformis, 75-76 in S. aureus, 76

Peptide bond formation, kinetics of, 454 Phage(s)

induction, 66 transducing, 34, 36-37

Phage biology, and promoter arrangement, 27 Phage lambda

antitermination in, 32-38 evolution of, 47-48 genes of lytic cycle, 33 N protein of, 264-265 regulatory protein gp cro, 37-38 repressor and operators, 247-248

Phage 17 mRNA, translation of, 371-373 Phage T4 gene 32 protein, repression of, 370 Phage T7, see Bacteriophage Phenylalanine, as regulator in aromatic acid bio­

synthesis, 124, 125, 128, 129 Phenylpyruvate, as regulator in aromatic acid

biosynthesis, 129 cPX174 A protein, active and inactive mRNAs for,

373 cPXI74 Bacteriophage, codons used in, 382 6-Phosphogluconate dehydrogenase, 90 Plasmids, 89-90

self-replicating, 47 Plastids, as regulators of catabolic pathways,

144-145 Pleiotypic response

and RNA synthesis inhibition, 408-409 and stringent response, 408

Polarity in gene clusters, 42 genetic, 34-36 mutational, 459 relief from, 36 suppressors of, 458-459 and transcription-translation coupling, 457-459

Polarity effect, in RNA bacteriophage, 371 Polarity suppression, and extragenic suppressors,

438 Polypeptide chain elongation, sequences directing,

379-384 Polypeptide chain growth rate, 493 Polypeptide chain initiation, messenger binding

during, 358 Polypeptide chain termination, 441-449

sequence of, 446 Positive control systems, with regulator molecule,

112 Posttranscriptional modifications, changes in, 423 ppGpp

as effector, 534

ppGpp (cont.) levels of, 495 and PSS regulation, 495, 520-534 and ribosome synthesis, 525, 534 and RNA accumulation rate, 521 role in stringency mechanism, 14

ppGpp concentrations during transients, 523-525 steady state, 521-523

ppGpp-dependent transcription, and histidine, 414-415

ppGpp synthesis and his T mutants, 412 and stringent factor, 405-406 and uncharged tRNA, 405-407

Probability of base sequences, 295-299 chemical randomness of, 300 plot of log of, 299, 303 variance of, 299-300

Probability of partially correct sequences, 301-303 Probability studies of mistranslations per codon,

451 Proflavin

and frameshift mutations, 440 and intercalation with DNA, 176 suppressor of, 440

Proflavine, chemical structure of, 177 Prokaryotes

genetic regulation in, 1-17 methodology for genetic studies of, 50-51 operon regulation in, 12

Promoter(s), 2, 4, 19, 121-122 activator binding in, 242 in bacteriophage T7, 31-32 basic, 233 characteristics of, 231-232 definition, 231 function, 233-235 and gene transcription, 27 genes transcribed from, 23-30 internal, 21-23 internal, E. coli, 49 lambda, 34 melting, 238-239 mUltiple, 31-32 mutations of, 191 overlapping, 45 PRE, 26 regulation of, 32, 231-250 and repressor-operator systems, 244-246 seq uences, 234 and sigma factor replacement, 249-250 "silent," 249 strength of, 236 transition temperature, 238 and translational control, 32 Irp, origins of, 49 truncated, 237 utilization, 232

Promoter activation definition, 242 effector-induced, 243 effector-mediated, 245 model, 242-243

Promoter efficiencies, 510-512 Promoter-polymerase interaction, elements of, 191

Promoter sites abnormal, 239 evolution of, 121-122

Promoter strength, 498 differences in, 240 and melting rate, 241 and recognition, 241 and RS complex formation rate, 240 and sequence information organization, 242

Prophage(s) inducible, 62, 65-66 replication of, 65

Prophage lambda as activator, 77 induction of, 76-77 as repressor, 77

Propidium, chemical structure of, 177 Protein(s)

accessory, 512-513 activator, and autogenous regulation, 68, 79 antitermination, 264-267 bifunctional, 97 catabolite repressor, see CAP-cAMP system;

CAP protein; catabolic gene activator pro­tein; cyclic AMP receptor protein

cis-acting, 50-51 core

active control of, 498 passive control of, 498 synthesis rates, 497

dnaB,206-207 dnaC,207 multifunctional, 48n, 97 purified, heterogeneic amino acid sequences in,

451 r-, synthesis rates, 497 regulatory, 5-8, 15-16,41

activator, 5 aporepressor, 5 molecules affecting, 5-6 repressor, 5

repressor, and autogenous regulation, 68, 79 scaffOlding, 96 sigma, 249 structures and functional groups

dipolar interactions, 284 hydrogen-bonding groups, 283 hydrophobic groups, 283 positively charged residues, 282-283 stacking interactions, 283-284

transcriptional, 279-343 unwinding, 94-96

Protein discrimination, 293-295 Protein-DNA interactions

redundant, 229 sequence-specific

binding energy of, 223-224 effectors, 222-223 ionic bonds, 223-224 model of, 226-227 mUltiple contacts, 221 reversibility, 222-223 reversible binding, 224-225 ruler concept, 226 signal finding, 222 specific/nonspecific interactions, 221-222

553

INDEX

554

INDEX

Protein-DNA interactions (cont.) sequence-specific (cont.)

tight complexes, 222-223 and symmetry arguments, 173

Protein-effector complex, affinity for DNA con­trol sequences, 222-223

Protein evolution, and gene fusion, 123 Protein· mRNA interaction, and chain termina­

tion, 441 Protein-nucleic acid binding

methods for studying, 306-308 overlapping, 307 parameters of, 306, 307

Protein-nucleic acid interactions conformational basis of, 281-282 electrostatic component, 307 molecular bases of, 281-293

Protein-nucleic acid recognition interactions, structural features useful in, 291-293

Protein-oligonucleotide binding constant, 307 Protein recognition matrix, multisite, 289-291 Protein synthesis, 2

constitutive, 510-512 effect of growth rates on, 503 inhibition, and DNA synthesis inhibition, 204 at low growth rates, 500-504 nonfunctional, selective disadvantage of, 161 of tRNA, 403-404 at varied growth rates, 496-500

Protein-synthesizing system (PSS) biosynthetic enzyme genes of, 492 catabolic enzyme genes of, 492 cell-free, 421 core genes of, 491 efficiency loss of low growth rates, 50 I genes dependent on, 490 levels of control of, 489-490 ppGpp regulation of, 495, 520-534 properties of, 519-520 regulation of, 487-537

and transcription patterns, 496 stable RNA genes of, 491-492 transcription of, 489-490

Protocatechuate pathways, 138-141 enzymes of, 140-141 regulatory genes of, 138-140

Pseudomonas aeruginosa, 118, 119 arginine genes of, 116 arrangement of histidine genes in, 116-117 catabolite repression in, 147 and dual enzyme functions during evolution,

116 growth on aliphatic amides, 150 inducer in, 113 transductional analysis, 143 tryptophan biosynthesis in, 131-132

Pseudomonas pUlida, 74-75, 118, 119 growth on aliphatic amides, 150 /3 -ketoadipate pathway in, 134

regulation of, 139 meta pathway enzymes in, 142-143 plasmids in, 145 transductional analysis, 143 tryptophan biosynthesis in, 131-132

Pseudomonas species aromatic pathway enzymes in, 129 catabolic gene arrangements in, 144

Pseudomonas aeruginosa (cont.) catabolite repression control in, 152 mandelate enzymes in, 135-137

Pseudooperator, sequence of, 193-194 Pseudouridine

and "frozen" tRNA, 416 and histidine operon derepression, 412 regulation of amino acid biosynthesis, 412

PSS, see Protein-synthesizing system

R 17 A protein initiator region, 367 R 17 coat protein, as translational repressor, 369 Random occurrence of base pairs, plots of, 299,

303 Rapid-start (RS) complex

core contacts in, 240 energy input, 236 ' formation of, 235-236 formation rate, 240 maintenance of, 236-237 and melting in, 232, 233-234 polymerase-promoter interactions in, 236 and promoter strength, 240 and sigma recognition, 236 specific/unspecific contacts in, 239-240 temperature dependence of, 238-239 on truncated promoter, 237

Recognition in promoter utilization, 233-234 sequence discrimination in, 235-236 thermodynamic aspects of, 303-306

Recognition complex, 237-238 requirements for, 250 role of, 239

Recognition sites, in antitermination, 40-41 Recombination

active form of DNA in, 190-192 and DNA unwinding, 190 energy needs of, 190-191 role of /3-kinked DNA in, 190-191

Regulation, see Genetic regulation by activators, 58 autogenous, 3, 11-l2, 58

in inducible catabolic systems, 68 classical, in inducible catabolic systems, 68 definition, I of enzyme synthesis, 111-114

catabolite repression, 13-14, 112 "glucose effect," 112 negative control, 112 operon theory, 112

by feedback loop, l2 informational aspects of, 295-303 level of initiating chromosome replication,

204-205 theorems, 98 tRNA as target for, 419-424 tRNA role in, 401-426

Regulative assembly. See Repair replication Regulator(s)

as activators, 58 of arabinose operon, 89 evolution of, 116-121 predictable nature of, 62-64 repressive function of, 58 synthesis of, 58-59

Regulatory genes in aromatic acid biosynthesis, 124, 125-126

ancestors of, 126 evolution of

in P. aeruginosa, 139-140 in P. pu/ida, 138-139

evolutionary potential of, 149 and map positions, 114

Regulatory mechanisms integration of, 12-14 stringency, 14, 405-409, 526

Regulatory molecules activator, 5 aporepressor, 5 corepressor, 5 inducer, 5-6 initiator, 4-5 operator, 4-5, 7-10 promoter, 4, 7-10 proteins, 5-8 repressor, 5

Regulon, II Reinitiation, 375 Relaxed syndrome, 525-527 Release factors

ribosomal components for, 443 in termination, 442-444

Repair replication, 210 Replicase synthesis, and phage coat protein,

368-369 Replication

active form of QNA in, 190-192 characteristics of, 220 control signals, 220 and DNA unwinding, 190 energy needs of, 190-191 modes of, 65 role of {3-kinked DNA in, 190-191

Replication complex, 205-208 destruction of, 208-210 disposable, 209 effect of growth conditions on, 208, 209 function in absence of DNA synthesis, 207 inactivation and temperature changes, 206 inhibition of, 209 restricted action by stoichiometry, 208-209 reusable, 206, 209

Replicon(s), 89 multiple in all euka, .)tes, 205 tandem arrangemen t of, 205

Replicon hypothesis, and DNA synthesis, 204-205 Repressible systems

arginine, 82 drug sensitivity, 86-87

erythromycin, 87-88 tetracycline, 87

effectiveness criteria for, 77-78 histidine, 83-84 isoleucine-valine

in E. coli, 84-85 in Saccharomyces cerevisiae, 85-86

predictions for, 79 regulation, 79 tryptophan, 79-82

Repression, 8-11 catabolite, 7, 13-14, 112 cumulative, 9-10

Repression (cont.) establishment of, 27-28 multivalent, 9-10 natural advantage of. 10-11 negative control of, 9 and nitrate reductase, 73-74

Repression mechanisms in arginine synthesis, 63 selective advantage of, 10, 63 in tryptophan synthesis, 63

Repressor, 5, 8 autogenously regulated, 67 control of antibiotics, 65 formation following infection, 25 inactivation of, 23 lac, 19-20

induction of, 73 synthesis of, 73

synthesis of, 23-27, 38 thermolabile, 23 unregulated, 67

Repressor binding, 245 lac operator modifications effect on, 314

Repressor-inducer complexes, interactions with nonoperator DNA, 317-319 with operator, 317

Repressor-mediated control, 489 Repressor-operator binding, and effector

molecule, 246 Repressor-operator-inducer-nonoperator-DNA

system, model of, 322, 329 Repressor-operator systems, 244-246 Repressor proteins

biochemical characterization of, 466 sequences of, 374

Repressors, 59-66 and transcription blockage, 222-223

Restart polypeptides, 374 Restart signals, 374-375 Restriction point, 408 Reverse transcriptase, tRNA as primer for, 425 Rho ATPase, 259 RhO-dependent termination

and braking, 259-260 complex destabilization, 258-259 polymerase-rho interactions, 259 RNA and rho ATPase, 259 and RNA hairpin structure, 260 and simultaneous events, 259-260

Rho factor, 91-93 and terminators, 250-251

Rhodopseudomonas capsula/a, inhibition by lysine and threonine, 160-161

Ribitol blockage of catabolic pathway of, 155-156 catabolism, 155 metabolism, 154

Ribitol dehydrogenase, 154 Ribosomal mutations, 456-457 Ribosomal proteins, synthesis rate, 494-495 Ribosomal suppression, 438 Ribosomal suppressors, cistron-specific, 456-457 Ribosome(s)

binding sites of, 351 history of, 350-351 and initiation signal recognition, 350-379 at low growth rates, low efficiency of, 532-534

555

INDEX

556

INDEX

Ribosome(s) (cont.) thermophilic, 361

Ribosome-binding sites mutations in, 375-377 wild type, 384

Ribosome function, RNA· RNA interactions in, 384-387

Ribosome structure, alterations of, 454 Ribosome synthesis

and cell cycle, 535-537 and ppGpp, 534

Rigid nucleotide concept, 284-285 Ring closure event, 335n RNA

chain elongation, 240 hairpin structure, 253, 256, 258

and trp attenuator, 263-264 polymerase, 2-3, 5 and replication initiation, 211-212 secondary structure, 15 terminated, 253

see also MRN A RN A bacteriophages, polarity effect, 371 RNA chain growth rates, 493 RNA elimination, 257-258 RNA-induced pausing. See Braking RNA-P, see RNA polymerase RNA phage initiation sites, structural effects, 367 RN A phage messengers, and secondary structure,

366-367 RN A polymerase

allosteric effector for, 405 and ,B-kinked DNA recognition, 191 core units per cell, 513 dissociation, 253-255 melting in, 280 modification of, 248 as promoter site primers, 514 quantitative assessments of, 513 -rho interactions, 259 and sigma factor association, 232 terminator DNA interactions, 253-255

destabilization of, 259 RNA polymerase activity, 407-408 RNA polymerase binding, integration with control

of the lactose operon, 339-340 RNA polymerase-promoter complex, open and

closed formation, 337-340 RNA polymerase-promoter interaction, 337-339 RNA· RNA interactions, in ribosome functions,

384-387 RNA secondary structure, regulation by, 370-371 RN A synthesis

and gene function, 212 inhibition, and DNA synthesis inhibition, 204

RNA transcription, nucleotide sequence control of, 192

RS, see Rapid-start complex Ruler concept of protein, 226

S I binding sites, 370 Saccharomyces cerevisiae, 63, 64

biosynthesis in, 85-86 enzyme regulation studies in, 148-149 genetic analysis of, 469

Saccharomyces cerevisiae (cont.) isoleucine-valine biosynthesis in, 85-86 mutations in, 469 nonsense suppressors in, 470 restriction point in G-I phase of, 409

Salmonella typhimurium, 40 and autogenous regulation, 71 bioregulators in, 83 frameshift suppression in, 437, 439 genetic loci on chromosomes of, 203-204 histidine biosynthesis in, 83 histidine operon of, 23 histidine utilization system in, 71 and nitrogen limitation, 147 regulatory systems for histidine biosynthetic

enzymes in, 113 trp operon of, 21

Scaffolding proteins, 96 Schizosaccharomyces pombe

genetic analysis of, 469 nonsense suppressors in, 470

Sequence-specific interactions and multiple DNA contacts, 221 signals for, 222 specific I nonspecific, 221-222

Shift-down transients protein synthesis during, 527-532 ribosome synthesis during, 527-532

Shift experiments, 534 Shine and Dalgarno hypothesis, test of, 356 Sigma factor

association with RNA polymerase, 232 function of, 232-233 replacement, 248-250

Sigma recognition and promoter DNA, 237 and RS complex formation, 236-237

Solenoids models of, 188-189 origin of, 187

Soluble RNA, see tRNA SOS repair, see Error-prone repair system Species specificity, RNA vs. proteins in, 361-363 Specificity

of DNA, sequence determined, 221 in lac operon, 112

SRNA, see tRNA Stable RNA, partitioning of, 493-494 Stacking interactions, and nucleic acid stability,

283-284 Staphyloccus aureus

erythromycin resistance in, 75 natural inducer of, 76 penicillin resistance in, 65 penicillinase system in, 76

Streptomyces coelicolor, methylenomycin synthesis by, 117

Streptomycin, and translational fidelity, 454-455 Stringency, characteristics of, 14 Stringent control, 14, 526

conditions for study of, 405 definition, 405 in eukaryotes, 408 pleiotropic effect of, 405 position effect of, 405 primary role of, 408

Stringent factor, 14 and ppGpp biosynthesis, 405

Stringent response and deacylation of tRNA, 409 in E. coli, 408-409 mediators of, 16 and relA gene, 14

Structural genes, linkage of, I 16 Structural rigidity, and protein-nucleic acid

interaction, 293 Substrates

and macromolecular syntheses, 504-507 novel, for evolutionary studies, 149-150

Sugar-operon modulating system, 280 Super helix formation, and protein-nucleic acid

interaction, 29 I Superrepressors, 72 Suppression, 433-475

efficiency of, 447-449 in eukaryotes, 434 extragenic, 435 frameshift, 437 history of, 435-436 intragenic, 435 missense, 437 nomenclature standardization, 436 nonsense, 433, 436-437 polarity, 438 ribosomal, 438

Suppression efficiency, quantitation of, 448 Suppressor mutations, isolation of, 472 Suppressor tRNA

mischarging, 463-466 structure-function relationships, 463-466

Suppressors, genetic analysis of, 46 I Symmetry

base sequence, 173 crystallographic point group, 173 departures from, 173 and dyad axes, 172

Synthetic activities, and PSS regulation, 490-492

T antigen, autogenous regulation of, 90-91 T ----+ A sequence, stability, 254 Tandem sequences, and base sequence probability,

298 Telestability, and kinked DNA, 191-192 Templates, bifunctional recognition, 289 Termination

and attenuators, 39-40 polypeptide chain, 441 rho-dependent, 36-37, 258-260 rho-mediated, 34, 35 role of release factors in, 442-444 and terminator codon recognition, 442 of transcription, 9 I

Termination points, 252-253 and RNA hairpin structure, 257

Termination signals, 447 Terminator(s), 3, 250-261

braking, 255-257 "early," 256 DNA melting, 257 functions of, 250 rho-dependent, 25 I and rho factor, 250-251

Terminator(s) (cont.) rho-independent, 251 strength, 26 I strong, 253 structure, 252 symmetry, 253 transcription, 260-261

Terminator codons recognition of, 442 tandem, 445

Terminator contacts, kinetics of, 255 Terminator mutation, 250 Terminator regulation

and rho factor, 26 I -262 and termination point change, 26 I translational, 262

Terminator sequences, polar types, 260-261 Tests, cis / trans, 50 Tetracycline

induced resistance to, 65, 75 repressed sensitivity to, 87 repressor protein control of, 65

Threonine deaminase biregulator role for, 84-85 repression of, 85

Transaminase, dual function in aromatic acid pathways, 129

Transcript digestion, by RNAse, 260 Transcript termination, 260-26 I

and rho mutations, 260 Transcription

active form of DNA in, 190-192 attenuated, 21 bidirectional, 45 cl,24 of circular DNA, 2 control of, 220, 23 I correction mechanisms in, 433 coupled with translation, 83 definition, 2 I 9 development, 230-23 I divergent, 21, 4 I -45 and DNA unwinding, 190 energy needs of, 190- 191 in gene clusters, 4 I -43 initiation of, 232 initiation studies, 512-520 maintenance, 230-23 I overlapping, 21, 46 from PI., 28 frompRM,25 patterns of, 495-520 in phage lambda, 33-36 phage-specific, 33 of protein-synthesizing control, 489-490 rate-limiting step in, 239 regulatory mechanisms of, 267-268 repressor blockage of, 222-223 role of {3-kinked DNA in, 190- I 9 I termination, 91-93 trp,38 unit, 230

Transcription attenuation, 489 Transcription development, 230

regulation with new RNA polymerase, 250 by sigma replacement, 249

557

INDEX

558

INDEX

Transcription frequencies, 507-520 Transcription-translation coupling, 508-510 Transcription-translation system, coupled, 415 Transcription unit

with operator sequence, 245 terminator in, 250

Transcriptional control in eukaryotes, 280-281 of genome function, 279-281

Transcriptional proteins, interaction specificity of, 279-343

Transfer RNA, see tRNA Transferase, and cAMP, 40 Translation, 220

correction mechanisms in, 433 errors in, 354-357 modulation of, 418-419 tRNA-dependent modulation of, 419-424

Translation frequencies, 507-520 Translational control, 14-15

at molecular level, 368-373 Translational efficiency, correlation with

mRNA . rRNA complementary, 378 Translational initiation, mutants affecting, 375 Translational reinitiation, and primary polar

mutation, 438 Translational repressors, proteins as, 368-370 Translational restarts, 373-375 Transmitter region, as binding site, 120 Transport proteins, 505 Transposons, and drug resistance, 144 tRNA

and arrested cell growth, 409 and base pair formation, 425 biosynthesis of, 402-403, 461-463 charged, 405-406 cloverleaf structure of, 402 codon-dependent translational selectivity, 421 deacylation of, 409 discovery of, 401-402 forms of, 405 genetics of, 459-461 involvement other than protein synthesis, 402 location of, 402-403 mischarging mutants, 464-466 modification of, 403 in protein synthesis, 403-404 redundant, 437 as regulation target, 419-424 as regulatory molecule, 404-419

operon-specific control, 410 stringent control, 405-410

role in regulation, 401-426 size reduction of, 403 structural role in packaging viral RNA, 425 transcriptional product of, 403 undermodified, 451

tRNA anticodons, pairing control of, 452 tRNA biosynthesis

enzymes of, 462 schema of, 462

tRNA complexes, dimeric, 452 tRNA maturation

and endonucleases, 403

tRNA maturation (cont.) half-life of intermediates of, 403 modifications in, 403 mutants affecting, 403 size reduction, 403

tRNA modification, effect on codon specificity, 449-451

tRN A population changes, analysis of, 422 tRN A structural genes, mutations in, 459 tRNA suppressors, efficiencies of, 438 trp attenuator

control, 262-263 gene regulation, 262 model, 263-264

trp genes regulatory switches, 262 and tryptophan levels, 262

trp mRNA, hybridizations of, 457 trp operon, 514-517

and rho factor, 418 Tryptophan

absorption, 63 and autogenous regulation, 80 as corepressor, 80 E. coli enzymes for, 80 as regulator in aromatic acid biosynthesis, 124,

125, 128, 129 in repressible biosynthetic systems, 79-82 synthesis of, 8-9, II

Tryptophan biosynthesis feedback inhibition in, 131-132 gene-enzyme relationship in, 130-132

in Acinetobacter calcoaceticus, 131, 132 Bacillus subtilis, 131, 132 in E. coli, 130-131 in Neurospora, 131 in Pseudomonas aeruginosa, 131-132 in Pseudomonas pUlida, 131-132

repression control in, 132 Tryptophan operon, tRNAT,p regulation of, 416-

417 Tryptophan synthase, 74-75

and autogenous regulation, 75 Tumor cells, tRNA changes in, 423-424 Two-operon hypothesis

and cis-specific proteins, 51 in E. coli biotin cluster, 43-45

Tyrosine, as regulator in aromatic acid biosynthesis, 124, 125, 128, 129

Ultraviolet light, mutagenic effect of, 210 Unique sequences, overspecification of, 305 Unwinding protein, function, 94-95

Viral RNA, 425-426

Wobble hypothesis and nonstandard base pairs, 449, 452-453 and undermodified tRNA, 451

Xylitol, novel pathway for catabolism of, 158

Yeast, tRNA-mediated suppression in, 469-472 Yeast suppressor strains, genetic analysis of,

471-472