Molecular Cell Biology Harvey Lodish, Arnold Berk, Lawrence S. Zipursky, Paul Matsudaira, David Baltimore and James Darnell Fourth Edition, 2000, W. H. FREEMAN Acknowledgments About the Authors Preface Supplements 1. The Dynamic Cell 1.1. Evolution: At the Core of Molecular Change 1.2. The Molecules of Life 1.3. The Architecture of Cells 1.4. The Life Cycle of Cells 1.5. Cells into Tissues 1.6. Molecular Cell Biology: An Integrated View of Cells at Work 2. Chemical Foundations 2.1. Covalent Bonds 2.2. Noncovalent Bonds 2.3. Chemical Equilibrium 2.4. Biochemical Energetics 2.5. Activation Energy and Reaction Rate Testing Yourself on the Concepts MCAT/GRE-Style Questions References 3. Protein Structure and Function 3.1. Hierarchical Structure of Proteins 3.2. Folding, Modification, and Degradation of Proteins 3.3. Functional Design of Proteins 3.4. Membrane Proteins 3.5. Purifying, Detecting, and Characterizing Proteins PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 4. Nucleic Acids, the Genetic Code, and the Synthesis of Macromolecules 4.1. Structure of Nucleic Acids 4.2. Synthesis of Biopolymers: Rules of Macromolecular Carpentry 4.3. Nucleic Acid Synthesis 4.4. The Three Roles of RNA in Protein Synthesis 4.5. Stepwise Formation of Proteins on Ribosomes PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 5. Biomembranes and the Subcellular Organization of Eukaryotic Cells 5.1. Microscopy and Cell Architecture 5.2. Purification of Cells and Their Parts 5.3. Biomembranes: Structural Organization and Basic Functions 5.4. Organelles of the Eukaryotic Cell PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 6. Manipulating Cells and Viruses in Culture 6.1. Growth of Microorganisms in Culture 6.2. Growth of Animal Cells in Culture 6.3. Viruses: Structure, Function, and Uses PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 7. Recombinant DNA and Genomics 7.1. DNA Cloning with Plasmid Vectors 7.2. Constructing DNA Libraries with λ Phage and Other Cloning Vectors 7.3. Identifying, Analyzing, and Sequencing Cloned DNA 7.4. Bioinformatics 7.5. Analyzing Specific Nucleic Acids in Complex Mixtures 7.6. Producing High Levels of Proteins from Cloned cDNAs 7.7. Polymerase Chain Reaction: An Alternative to Cloning 7.8. DNA Microarrays: Analyzing Genome-Wide Expression PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 8. Genetic Analysis in Cell Biology 8.1. Mutations: Types and Causes 8.2. Isolation and Analysis of Mutants 8.3. Genetic Mapping of Mutations 8.4. Molecular Cloning of Genes Defined by Mutations 8.5. Gene Replacement and Transgenic Animals PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 9. Molecular Structure of Genes and Chromosomes 9.1. Molecular Definition of a Gene 9.2. Chromosomal Organization of Genes and Noncoding DNA 9.3. Mobile DNA 9.4. Functional Rearrangements in Chromosomal DNA 9.5. Organizing Cellular DNA into Chromosomes 9.6. Morphology and Functional Elements of Eukaryotic Chromosomes 9.7. Organelle DNAs PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 10. Regulation of Transcription Initiation 10.1. Bacterial Gene Control: The Jacob-Monod Model 10.2. Bacterial Transcription Initiation 10.3. Eukaryotic Gene Control: Purposes and General Principles 10.4. Regulatory Sequences in Eukaryotic Protein-Coding Genes 10.5. Eukaryotic Transcription Activators and Repressors 10.6. RNA Polymerase II Transcription-Initiation Complex 10.7. Molecular Mechanisms of Eukaryotic Transcriptional Control 10.8. Other Transcription Systems PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 11. RNA Processing, Nuclear Transport, and Post-Transcriptional Control 11.1. Transcription Termination 11.2. Processing of Eukaryotic mRNA 11.3. Regulation of mRNA Processing 11.4. Signal-Mediated Transport through Nuclear Pore Complexes 11.5. Other Mechanisms of Post-Transcriptional Control 11.6. Processing of rRNA and tRNA PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 12. DNA Replication, Repair, and Recombination 12.1. General Features of Chromosomal Replication 12.2. The DNA Replication Machinery 12.3. The Role of Topoisomerases in DNA Replication 12.4. DNA Damage and Repair and Their Role in Carcinogenesis 12.5. Recombination between Homologous DNA Sites PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 13. Regulation of the Eukaryotic Cell Cycle 13.1. Overview of the Cell Cycle and Its Control 13.2. Biochemical Studies with Oocytes, Eggs, and Early Embryos 13.3. Genetic Studies with S. pombe 13.4. Molecular Mechanisms for Regulating Mitotic Events 13.5. Genetic Studies with S. cerevisiae 13.6. Cell-Cycle Control in Mammalian Cells 13.7. Checkpoints in Cell-Cycle Regulation PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 14. Gene Control in Development 14.1. Cell-Type Specification and Mating-Type Conversion in Yeast 14.2. Cell-Type Specification in Animals 14.3. Anteroposterior Specification during Embryogenesis 14.4. Specification of Floral-Organ Identity in Arabidopsis PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the concepts MCAT/GRE-Style Questions References 15. Transport across Cell Membranes 15.1. Diffusion of Small Molecules across Phospholipid Bilayers 15.2. Overview of Membrane Transport Proteins 15.3. Uniporter-Catalyzed Transport 15.4. Intracellular Ion Environment and Membrane Electric Potential 15.5. Active Transport by ATP-Powered Pumps 15.6. Cotransport by Symporters and Antiporters 15.7. Transport across Epithelia 15.8. Osmosis, Water Channels, and the Regulation of Cell Volume PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 16. Cellular Energetics: Glycolysis, Aerobic Oxidation, and Photosynthesis 16.1. Oxidation of Glucose and Fatty Acids to CO2 16.2. Electron Transport and Oxidative Phosphorylation 16.3. Photosynthetic Stages and Light-Absorbing Pigments 16.4. Molecular Analysis of Photosystems 16.5. CO2 Metabolism during Photosynthesis PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 17. Protein Sorting: Organelle Biogenesis and Protein Secretion 17.1. Synthesis and Targeting of Mitochondrial and Chloroplast Proteins 17.2. Synthesis and Targeting of Peroxisomal Proteins 17.3. Overview of the Secretory Pathway 17.4. Translocation of Secretory Proteins across the ER Membrane 17.5. Insertion of Membrane Proteins into the ER Membrane 17.6. Post-Translational Modifications and Quality Control in the Rough ER 17.7. Protein Glycosylation in the ER and Golgi Complex 17.8. Golgi and Post-Golgi Protein Sorting and Proteolytic Processing 17.9. Receptor-Mediated Endocytosis and the Sorting of Internalized Proteins 17.10. Molecular Mechanisms of Vesicular Traffic PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 18. Cell Motility and Shape I: Microfilaments 18.1. The Actin Cytoskeleton 18.2. The Dynamics of Actin Assembly 18.3. Myosin: The Actin Motor Protein 18.4. Muscle: A Specialized Contractile Machine 18.5. Actin and Myosin in Nonmuscle Cells 18.6. Cell Locomotion PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 19. Cell Motility and Shape II: Microtubules and Intermediate Filaments 19.1. Microtubule Structures 19.2. Microtubule Dynamics and Associated Proteins 19.3. Kinesin, Dynein, and Intracellular Transport 19.4. Cilia and Flagella: Structure and Movement 19.5. Microtubule Dynamics and Motor Proteins during Mitosis 19.6. Intermediate Filaments PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 20. Cell-to-Cell Signaling: Hormones and Receptors 20.1. Overview of Extracellular Signaling 20.2. Identification and Purification of Cell-Surface Receptors 20.3. G Protein –Coupled Receptors and Their Effectors 20.4. Receptor Tyrosine Kinases and Ras 20.5. MAP Kinase Pathways 20.6. Second Messengers 20.7. Interaction and Regulation of Signaling Pathways 20.8. From Plasma Membrane to Nucleus • PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 21. Nerve Cells 21.1. Overview of Neuron Structure and Function 21.2. The Action Potential and Conduction of Electric Impulses 21.3. Molecular Properties of Voltage-Gated Ion Channels 21.4. Neurotransmitters, Synapses, and Impulse Transmission 21.5. Neurotransmitter Receptors 21.6. Sensory Transduction 21.7. Learning and Memory PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 22. Integrating Cells into Tissues 22.1. Cell-Cell Adhesion and Communication 22.2. Cell-Matrix Adhesion 22.3. Collagen: The Fibrous Proteins of the Matrix 22.4. Noncollagen Components of the Extracellular Matrix 22.5. The Dynamic Plant Cell Wall PERSPECTIVES for the Future • PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 23. Cell Interactions in Development 23.1. Dorsoventral Patterning by TGFβ-Superfamily Proteins 23.2. Tissue Patterning by Hedgehog and Wingless 23.3. Molecular Mechanisms of Responses to Morphogens 23.4. Reciprocal and Lateral Inductive Interactions 23.5. Overview of Neuronal Outgrowth 23.6. Directional Control of Neuronal Outgrowth 23.7. Formation of Topographic Maps and Synapses 23.8. Cell Death and Its Regulation PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References 24. Cancer 24.1. Tumor Cells and the Onset of Cancer 24.2. Proto-Oncogenes and Tumor-Suppressor Genes 24.3. Oncogenic Mutations Affecting Cell Proliferation 24.4. Mutations Causing Loss of Cell-Cycle Control 24.5. Mutations Affecting Genome Stability PERSPECTIVES for the Future PERSPECTIVES in the Literature Testing Yourself on the Concepts MCAT/GRE-Style Questions References Glossary ABCDEFGHIKLMNOPQRSTUVWXZ