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Contents Abbreviations How to use this book Preface 1. Biological Heredity and Variation Mendelian inheritance Segregation at one locus Segregation at two loci Quantitative inheritance 2. The Cell Cycle The bacterial cell cycle The eukaryotic cell cycle The molecular basis of cell cycleregulation Progress through the cell cycle Special cell cyclesystems in animals 3. Chromatin Nucleosomes Higher order chromatin organization Chromatin and chromosome function Molecular structure of the bacterial nucleoid 4. ix xi xii 1 1 2 8 11 21 21 23 26 28 33 35 35 38 39 42 Chromosome Mutation Numerical chromosome mutations Structural chromosome mutations 45 45 49 5. Chromosome Structure and Function 57 57 58 60 Normal chromosomes - gross morphology Special chromosome structures Molecular aspects of chromosome structure 6. Development, Molecular Aspects Differentiation Pattern formation and positional information The environment in development 65 7. DNA Methylation and Epigenetic Regulation 93 93 94 97 DNA methylation in prokaryotes DNA methylation in eukaryotes Epigenetic gene regulation by DNA methylation in mammals 8. The Gene The concept of the gene 65 72 75 103 103 vi Advanced Molecular Biology Units of genetic structure and genetic function Gene-cistron relationship in prokaryotes and eukaryotes Gene structure and architecture 9. Gene Expression and Regulation Gene expression Gene regulation Gene expression in prokaryotes and eukaryotes 10. Gene Transfer in Bacteria Conjugation Transformation Transduction 11. The Genetic Code An overview of the genetic code Translation Special properties of the code 12. Genomes and Mapping Genomes, ploidy and chromosome number Physico-chemical properties of the genome Genome size and sequence components Gene structure and higher-order genome organization Repetitive DNA Isochore organization of the mammalian genome Gene mapping Genetic mapping Physical mapping 13. Mobile Genetic Elements Mechanisms of transposition Consequences of transposition Transposons Retroelements 10 10 10 11 11 11 11 11 11 11 12 12 12 12 12 13 13 13 13 13 13 14 14 14 15 16 16 17 17 18 14. Mutagenesis and 1 1 1 1 1 1 1 1 1 15. Mutation and Selection 2 2 2 2 DNA Repair Mutagenesis andreplication fidelity DNA damage: mutation andkilling DNA repair Direct reversalrepair Excision repair Mismatch repair Recombination repair The SOS response andmutagenic repair Structural and functional consequences of mutation Mutant alleles and the molecular basis of phenotype The distribution of mutations andmolecular evolution Mutations in Genetic Analysis 2 Contents 16. Nucleic Nucleic Nucleic Nucleic Acid Structure acid primary structure acid secondary structure acid tertiary structure 17. Nucleic Acid-Binding Properties Nucleic acid recognition byproteins DNA-binding motifs in proteins RNA-binding motifsin proteins Molecular aspects of protein-nucleic acidbinding Sequence-specific binding Techniques forthe study of protein-nucleic acidinteractions 18. Oncogenes and Cancer Oncogenes Tumor-suppressor genes 19. Organelle Genomes 20. 23. 24. 223 223 226 231 235 236 237 243 244 246 249 253 254 258 263 Organelle genetics Organelle genomes 263 264 Plasmids Plasmid classification Plasmid replication and maintenance 271 273 21. The Polymerase Chain Reaction (PCR) 22. vii 271 279 Specificity of the PCR reaction Advances andextensions to basicPCR strategy Alternative methods for in vitro amplification 279 283 284 Proteins: Structure, Function and Evolution Protein primary structure Higher order protein structure Protein modification Protein families Global analysis of protein function 287 288 289 295 297 304 Protein Synthesis The components of protein synthesis The mechanismof protein synthesis The regulation of protein synthesis 313 Recombinant DNA and Molecular Cloning Molecular cloning Strategies for gene isolation Characterization of cloned DNA Expression of cloned DNA Analysis of gene regulation Analysis of proteins and protein-protein interactions 323 313 315 318 324 331 336 339 342 345 viii Advanced Molecular Biology In vitro mutagenesis Transgenesis: gene transfer to animals andplants 34 34 25. Recombination Homologous recombination Homologous recombination and genetic mapping Random and programmednonreciprocal recombination Site specific recombination Generation of immunoglobulin andT-cell receptor diversity Illegitimate recombination 36 36 37 37 37 37 38 26. Replication Replication strategy The cellular replisomeand the enzymology of elongation Initiation of replication Primers and priming Termination of replication The regulation of replication 3 38 39 40 4 4 4 27. RNAProcessing Maturation of untranslated RNAs End-modification and methylation of mRNA RNA splicing RNA editing Post-processing regulation 4 4 4 4 4 4 28. SignalTransduction Receptors and signaling pathways Intracellular enzyme cascades Second messengers Signal ddivery 4 4 4 4 4 29. Transcription Principles of transcription Transcriptional initiation in prokaryotes -basal and constitutive components Transcriptional initiation in eukaryotes -basal and constitutive components Transcriptional initiation -regulatory components Strategies fortranscriptional regulation in bacteria and eukaryotes Transcriptional elongation and termination 4 4 4 4 4 4 4 30. Viruses and Subviral Agents Viral infection strategy Diversity of replication strategy Strategies for viralgene expression Subviral agents 4 4 4 4 4 Index 4