Genes and the Environment

Book Cover......Page 1
Half-Title......Page 2
Title......Page 3
Copyright......Page 4
Contents......Page 5
Preface......Page 9
CHAPTER 1 Introduction: Genes and the Impact of the Environment......Page 11
1.1 Genes, Genotypes and Phenotypes......Page 12
1.2 Gene Activity and the Environment......Page 13
1.3 Genes and the Tolerance of Environmental Stress......Page 14
1.4 DNA Stability and the Environment......Page 15
1.5 Scope of the Book......Page 17
1 GENE DAMAGE: Its LIMITATION, REPAIR and CONSEQUENCES......Page 18
CHAPTER 2 Environmental Factors that Damage DNA......Page 19
2.1 Synthetic Chemicals......Page 20
2.1.1 SOME CHEMICALS CAN ALKYLATE DNA......Page 21
2.1.2 SOME CHEMICALS ARE METABOLIZED TO DAMAGING ELECTROPHILIC REACTANTS......Page 22
2.2 Nuclear Radiation......Page 24
2.2.1 DAMAGE TO DNA BASES CAUSED BY NUCLEAR RADIATION......Page 29
2.2.2 DAMAGE TO DEOXYRIBOSE COMPONENTS OF DNA BY NUCLEAR RADIATION......Page 30
2.3.1 ULTRAVIOLET RADIATION AND THE OZONE LAYER......Page 33
2.3.2 ULTRAVIOLET DNA PHOTOPRODUCTS......Page 35
2.4 Atmospheric Pollutants......Page 36
2.4.2 SULPHUR DIOXIDE......Page 37
2.4.3 NITROGEN OXIDES......Page 38
2.4.4 AUTOMOBILE EXHAUST......Page 39
2.4.5 FORMALDEHYDE......Page 40
2.4.6 TOBACCO SMOKE......Page 41
2.5 Food Components......Page 42
2.5.3 HETEROCYCLIC AMINES......Page 43
2.5.4 PLANT PHENOLICS......Page 44
2.6.1 MITOMYCIN C......Page 46
2.6.2 NITROGEN MUSTARDS......Page 47
2.6.5 PSORALENS......Page 48
2.6.6 TOPOISOMERASE INHIBITORS......Page 49
2.7.1 VIRUSES......Page 50
2.8 Literature Sources and Additional Reading......Page 53
3.1 Gene Replication and ‘Proof-reading’ Mechanisms for Error Correction......Page 56
Copying DNA......Page 57
Unwinding DNA......Page 59
Priming the replication process......Page 60
The replication fork......Page 61
3.1.3 EXONUCLEASES AND THE CORRECTION OF ERRORS DURING NORMAL DNA REPLICATION: ‘PROOF-READING’......Page 63
3.2 Errors during DNA Replication Arising from Base Tautomerization......Page 65
3.3 Errors due to Deamination of DNA Bases......Page 66
3.4 The Spontaneous Loss of Bases from DNA......Page 67
3.5 Literature Sources and Additional Reading......Page 71
4.1 Neutrophils, Macrophages and the Oxidative Burst......Page 72
4.2 Superoxide Generation and Release from Non-phagocytic Mammalian Cells......Page 74
4.3.2 CHLOROPLASTS......Page 75
4.3.5 XANTHINE OXIDASE......Page 76
4.4 Singlet Oxygen......Page 77
4.5 Nitric Oxide......Page 78
4.6.1 FENTON-TYPE OXIDANTS......Page 79
4.6.3 LIPID PEROXIDATION......Page 81
4.7 The Extent of Oxidative Damage to DNA......Page 83
4.8 Literature Sources and Additional Reading......Page 84
CHAPTER 5 Detoxification and Antioxidant Defences......Page 86
5.1.1 CYTOCHROME P450 MIXED FUNCTION OXIDASES......Page 87
5.1.3 GLUTATHIONE S-TRANSFERASES......Page 89
5.1.4 ALDEHYDE-METABOLIZING ENZYMES......Page 90
Aldo-keto reductases (ALRDs)......Page 91
5.2 Cellular Antioxidant Defence Systems......Page 92
Superoxide dismutases......Page 93
Catalases......Page 94
Ascorbate peroxidases......Page 95
Glutathione reductases......Page 97
Ascorbic acid (vitamin C)......Page 98
Uric acid......Page 99
Flavonoids and polyphenolics......Page 100
5.3 Literature Sources and Additional Reading......Page 101
CHAPTER 6 DNA Repair Mechanisms......Page 103
6.2 Alkyltransferases......Page 104
6.3 Nucleotide Excision Repair......Page 105
6.4 Base Excision Repair Pathways......Page 107
6.5 Mismatch Repair......Page 109
6.6 Error-prone Replication......Page 111
6.7.1 REPAIR OF DOUBLE-STRAND BREAKS......Page 113
6.7.2 REPAIR OF SINGLE-STRAND GAPS......Page 114
6.8 Double-strand Break Repair......Page 115
6.9 Repair of Damage to Mitochondrial DNA......Page 116
6.10 Literature Sources and Additional Reading......Page 117
CHAPTER 7 Genetic Information Flow......Page 119
7.1 Transcription......Page 120
7.2 Translation......Page 123
7.3.1 PROMOTERS, RNA POLYMERASES AND SIGMA FACTORS......Page 126
7.3.3 OPERONS......Page 128
7.3.4 BACTERIAL OPERONS THAT CAN BE INDUCED OR REPRESSED BY ENVIRONMENTAL FACTORS......Page 129
7.4 Eukaryotic Genes—their Structure and Transcription......Page 131
7.5.1 TRANSCRIPTIONAL REGULATORY MECHANISMS......Page 134
7.5.2 THE ACCESSIBILITY OF EUKARYOTIC GENES WITHIN CHROMOSOMAL STRUCTURES......Page 135
7.5.3 POST-TRANSCRIPTIONAL PROCESSING OF THE PRIMARY GENE TRANSCRIPT......Page 136
7.5.5 TRANSLATIONAL CONTROL......Page 137
7.5.6 MRNA STABILITY......Page 138
7.6 DNA Control Sequences......Page 139
7.7 Literature Sources and Additional Reading......Page 140
CHAPTER 8 DNA Damage, Mutation, Cancer and Ageing......Page 141
8.1.1 CELL DIVISION CYCLE CHECKPOINTS......Page 142
8.1.2 DNA DAMAGE AND APOPTOSIS (PROGRAMMED CELL DEATH)......Page 145
8.2 Mutation......Page 147
8.2.1 TYPES OF MUTATION......Page 150
8.2.3 MUTATION RATE......Page 152
8.2.5 OXIDATIVE DAMAGE AND MUTATION......Page 153
8.2.6 TESTS FOR MUTAGENICITY......Page 154
8.2.7 MUTATION AT SPECIFIC GENETIC LOCI......Page 155
8.3 Human Diseases and Gene Repair......Page 156
8.4.1 PROTOONCOGENES AND ONCOGENES......Page 159
8.4.3 TUMOUR PROGRESSION......Page 161
8.5 The Environment and Cancer......Page 162
8.5.2 RADIATION......Page 163
8.5.5 VIRUSES......Page 165
8.5.7 DIET......Page 166
8.6 Markers of Cancer Risk from Environmental Carcinogens......Page 167
8.7 Ageing......Page 168
8.8 Literature Sources and Additional Reading......Page 169
2 ENVIRONMENTAL STRESS: GENOMIC RESPONSES......Page 173
CHAPTER 9 Gene Activation and Environmental Stress......Page 174
9.1.1 HEAT SHOCK PROTEINS......Page 175
9.1.2 THERMOTOLERANCE AND THE HEAT-SHOCK PROTEINS......Page 177
9.1.3 HEAT-SHOCK PROTEINS AS MOLECULAR CHAPERONES......Page 178
9.1.4 HEAT-SHOCK GENE ACTIVATION......Page 181
9.1.5 HSP70 AS A SENSOR OF NON-NATIVE PROTEINS AND REGULATOR OF HSP GENES......Page 183
9.1.6 PHYSIOLOGICAL INDUCERS OF HSP GENES......Page 184
9.2 Low-temperature Stress......Page 185
9.2.3 COLD ACCLIMATION AND LOW-TEMPERATURE RESPONSIVE GENES......Page 186
9.3.1 BACTERIA......Page 190
9.3.2 PLANTS......Page 192
9.3.3 WATER-RESPONSIVE GENES IN PLANTS......Page 193
9.4 Toxic Metal Stress......Page 194
Mercury......Page 195
Cadmium......Page 196
Metallothionein gene transcription......Page 197
The oxyR regulon......Page 200
The soxRS regulon......Page 201
9.5.2 EUKARYOTIC RESPONSES TO OXIDATIVE STRESS......Page 202
9.6.1 PLANTS......Page 204
9.6.2 MAMMALIAN TISSUES......Page 206
9.7.2 ULTRAVIOLET RADIATION STRESS IN PLANTS......Page 207
UVC......Page 208
UVA......Page 209
9.8 Toxic Chemical Stress......Page 210
9.8.1 ACTIVATION OF DETOXIFICATION ENZYME GENES......Page 211
9.8.2 MULTIDRUG RESISTANCE TRANSPORTER......Page 213
9.8.3 MIMICS AND INAPPROPRIATELY REGULATED GENE EXPRESSION......Page 214
9.9.1 RESPONSES TO NUTRIENT CHANGE IN BACTERIA......Page 217
9.9.2 NURIENT RESPONSES IN ANIMAL AND PLANT CELLS......Page 219
9.10 Pathogen and Wounding Stress......Page 221
9.11.1 HIGH-TEMPERATURE STRESS......Page 222
9.11.2 LOW-TEMPERATURE STRESS......Page 223
9.11.3 WATER STRESS......Page 224
9.11.5 OXIDATIVE STRESS......Page 225
9.11.7 ULTRAVIOLET RADIATION STRESS......Page 227
9.11.8 TOXIC CHEMICAL STRESS......Page 228
9.11.10 PATHOGEN AND WOUNDING STRESS......Page 229
CHAPTER 10 Stress Genes and Biotechnology......Page 230
10.1.2 CHILLING TOLERANCE......Page 231
10.1.4 DEHYDRATION TOLERANCE......Page 232
10.1.6 HERBICIDE TOLERANCE......Page 233
10.1.7 GENETICALLY MODIFIED ORGANISMS AND SAFETY......Page 234
10.2.1 CANDIDATE STRESS PROTEINS......Page 235
10.2.2 APPLICATIONS......Page 236
10.3 Genes from Organisms Living in Extreme Environments......Page 237
10.4 Bioremediation......Page 238
10.5 Literature Sources and Additional Reading......Page 241
3 THE ENVIRONMENT, GENES, BIODIVERSITY AND CANCER......Page 243
CHAPTER 11 Prospects......Page 244
11.1 Genes and Biodiversity......Page 245
11.2 Genes for Environmental Adversity......Page 246
11.3 The Environment, Gene Damage and Mutation......Page 247
11.4 Genes, Cancer and the Environment......Page 249
11.5 The Environment and Epigenetic Inheritance Mechanisms......Page 254
11.6 Environmental Stress Genes and Evolution......Page 255
11.8 Literature Sources and Additional Reading......Page 256
Index......Page 259