lHECELL A Molecular Approach, Fourth Edition Companion Website www.sinauer.com/ cooper The student website that accompanies The Cell, Fourth Edition is an invaluable tool that can help you master the material presented in the textbook through a variety of interactive resources. This robust site is available - i· to you free of charge, and features a wealth of study and review material coupled with multimedia content. The Cell: A Molocular Appro~h ...... L•"• S\ 31oio.l ~: ~-, • :_t & i ------ -------- .· .......... ·. ,_ - IC-11- ·- · Chapter 6: Replication, Mlintena1ce ald R~ ·- of Genomic DNA -~· -~· ·~' -~· ·~· ·~· ·~' ··-~·· ·_~_· __. . ·-" .. .~u __ ., -~· &I~ D t> ··-~·· A$ 1M ommunoglobiAin geMS!ftna...,llw8all ~and llwl~ngent>'l-~~thltllw~ dleln ~$Ill concalns lnC.......wng DNA~ IMVOJ Nglon ancllheo:onmnt Ngion. n.s.~ng ~ ...I ofiin 1M ONA.W splcwd 0<11 from RNA~ 1M~ Is tranteribed. - - ........ _,"" =- ~ Flglrol31-·•. ..• ••ol~ ~-p.nl THE COMPANION WEBSITE FEATURES THE FOLLOWING RESOURCES: • Online quiues that test your comprehension • Micrographs that illustrate cellular structures of each chapter (instructor registration required) and components • Problem sets that help you apply your • Web links for further study and research knowledge • Chapter summaries for a quick review of each • Narrated animations of key concepts and chapter processes described in the textbook • Complete glossary for easy access to • Videos showing cellular processes in action definitions of terms Website Animations 6.4~ ~ WEBSITE ANIMATION Throughout the book, you will see small boxes in the margins that refer to ""' specific website animations that are relevant to the topic being discussed. Heavy-Chain Genes ·.~ , Below is the full list of animations and the page on which they are refer During B cell development, site enced. On the website, you can go directly to any animation by entering the specific recombination joins regions of the immunoglobulin heavy-chain genes. animation number (e.g., 116.4") into the 11Book Link" box at the top of the leading to the production of unique page, and then pressing Enter. The website also contains videos, quizzes, immunoglobulin heavy chains. problems, and other resources that are not listed here. ANIMATION PAGE ANIMATION PAGE 1.1 • Cell Fractionation ______ 30 8.1 • Translation --------· 319 1.1 • Bond Formation 43 10.1 • Organization ofthe Golgi 411 1.1 • Passive transport 64 11.1 • From Proplastid to Chloroplast __ 458 3.1 • Catalysts and Activation Energy __ 74 11.1 • The Light Reactions 461 3.1 • Enzyme-Catalyzed Reactions 75 11.1 • Assembly of an Actin Filament __ 474 3.3 • Glycolysis 84 11.1 • A Thin Filament 492 3.4 • The Citric Acid Cycle ______ 86 11.3 • Microtubule Assembly----· 507 3.5 • The Calvin Cycle 92 11.4 • Kinesin 512 4.1 • Avery,Macleod,&McCarty 107 13.1 • A Chemical Synapse 547 4.1 • Bacterial Transformation 108 13.1 • The Sodium-Potassium Pump __ 552 4.3 • The ~~central Dogma" 113 13.3 • Endocytosis 557 4.4 • DNA Mutations 114 13.4 • Clathrin-Coated Pits and Vesicles 558 4.5 • HIV Reproduction 116 15.1 • Signaling by Secreted Molecules 600 4.6 • Restriction Endonucleases 118 15.1 • Signal Transduction 611 4.7 • Recombinant DNA Molecules 121 15.3 • Signal Amplification 619 4.8 • Sequencing a DNA Strand 126 16.1 • Phases ofthe Cell Cycle 650 4.9 • Polymerase Chain Reaction 131 16.1 • Embryonic Cell Cycles 651 4.10 • Nucleic Acid Hybridization 131 16.3 • Checkpoints in the Cell Cycle 655 4.11 • Southern Blotting 132 16.4 • Cyclins, Cdks, and the Cell Cycle _ 661 4.11 • Colony Hybridization 133 16.5 • Mitosis in an Animal Cell 670 4.13 • Monoclonal Antibodies 136 16.6 • Cytokinesis in Higher Plants _ 678 5.1 • Chromatin and Chromosomes __ 166 16.7 • Meiosis 679 6.1 • DNA Replication Fork 209 16.8 • Meiosis I and Mitosis Compared __ 679 6.1 • Homologous Recombination 229 16.9 • Prophase I of Meiosis 680 6.3 • Light-Chain Genes 234 16.10 • Polar Body Formation 683 6.4 • Heavy-Chain Genes _____ 234 17.1 • Apoptosis --------· 691 7.1 • Transcription 257 18.1 • Metastasis of a Cancer 724 7.1 • RNA Processing 290 18.1 • Density-Dependent Inhibition 725 THE CELL A Molecular Approach FOURTH EDITION - A Molecular Approach FOURTH EDITION GEOFFREY M. COOPER • ROBERT E. HAUSMAN Boston University I [fAI ASM Press ASM t Sinauer Associates, Inc. ~, Washington, D.C. Sunderland, Massachusetts PRESS The cover The cover illustrates the growth and maturation of blood cells. A cell extending processes is shown in the lower right and a cell undergoing apoptosis is in the lower left. The art.ist Chris Bickel is a professional medical illustrator residing near Washington, D.C. He specializes in visualizing and animating molecular and cellular biology. The Cell: A Molecular Approach, Fourth Edition Copyright© 2007 by Geoffrey M. Cooper. All rights reserved. This book may not be reproduced in whole or in part without permission. Address editorial correspondence to ASM Press, c/o The American Society for Microbiology, 1752 N Street NW, Washington, DC 20036 U.S.A. Address orders and requests for examination copies to Sinauer Associates, Inc., P.O. Box 407, 23 Plumtree Road, Sunderland, MA 01375 U.S.A. Phone: 413-549-4300 FAX: 413-549-1118 email: [email protected] www.sinauer.com Library of Congress Cataloging-in-Publication Data Cooper, Geoffrey M. The cell: a molecular approach I Geoffrey M. Cooper, Robert E. Hausman. - 4th ed. p.; ern. Includes bibliographical references and index. ISBN-13: 978-0-87893-219-1 (Sinauer Associates: hardcover) ISBN-10: 0-87893-219-4 (Sinauer Associates : hardcover) 1. Cytology. 2. Molecular biology. I. Hausman, Robert E., 1947- . II. Title. [DNLM: 1. Cells. 2. Cytology. 3. Molecular Biology. QU 300 C776c 2007] QH581.2.C66 2007 571.6-dc22 2006012935 Printed in U.S.A. 5432 This book is dedicated to Florence Haseltine, with thanks for having taught me how to do my first experiment. G.M.C. Brief Contents PART I INTRODUCTION 1 1 An Overview of Cells and Cell Research 3 2 The Composition of Cells 43 l Cell Metabolism 73 4 Fundamentals of Molecular Biology 103 PART II THEFLOWOFGENETICINFORMATION 153 5 The Organization and Sequences of Cellular Genomes 155 6 Replication, Maintenance, and Rearrangements of Genomic DNA 201 7 RNA Synthesis and Processing 253 8 Protein Synthesis, Processing, and Regulation 309 PART Ill CELLSTRUCTUREANDFUNCTION 353 9 The Nucleus 355 10 Protein Sorting and Transport: The Endoplasmic Reticulum, Golgi Apparatus, and Lysosomes 385 11 Bioenergetics and Metabolism: Mitochondria, Chloroplasts, and Peroxisomes 433 12 The Cytoskeleton and Cell Movement 473 11 The Plasma Membrane 529 14 Cell Walls, the Extracellular Matrix, and Cell Interactions 569 PART IV CELL REGULATION 597 15 Cell Signaling 599 16 The Cell Cycle 649 17 Cell Death and Cell Renewal 689 18 Cancer 719 Contents Preface xiv Organization and Features of The Cell xvi Media and Supplements to Accompany The Cell xviii Introduction PART 1 Viruses 36 Global Analysis of Protein Localization 68 • KEY EXPERIMENT Animal Cell Protein Interactions 69 Culture 35 • KEY EXPERIMENT The Folding of An Overview of Cells • MOLECULAR MEDICINE Viruses Polypeptide Chains 54 and Cancer 37 • KEY EXPERIMENT The Structure and Cell Research 3 Summary and Key Terms 39 of Cell Membranes 59 Questions 41 Summary and Key Terms 70 Tbe Origin and Evolution of Cells 4 References and Further Reading 41 Questions 71 The First Cell 4 References and Further Reading 71 The Evolution of Metabolism 7 2 Present-Day Prokaryotes 8 3 Eukaryotic Cells 9 The Origin of Eukaryotes 10 The Composition The Development of Multicellular Cell Metabolism 73 Organisms 12 of Cells 43 Cells as Experimental Models 16 The Central Role of Enzymes as E. coli 16 The Molecules of Cells 43 Biological Catalysts 73 Yeasts 17 Carbohydrates 44 The Catalytic Activity of Enzymes 73 Caenorhabditis elegans 17 Lipids 46 Mechanisms of Enzymatic Catalysis 74 Drosophila melanogaster 18 Nucleic Acids 50 Coenzymes 78 Arabidopsis thaliana 19 Proteins 52 Regulation of Enzyme Activity 79 Vertebrates 19 Cell Membranes 58 Metabolic Energy 81 Tools of Cell Biology 11 Membrane Lipids 60 Free Energy and ATP 81 Light Microscopy 21 Membrane Proteins 61 The Generation of ATP from Glucose 84 Electron Microscopy 27 Transport across Cell Membranes 63 The Derivation of Energy from Other Subcellular Fractionation 30 Proteomics: Large-Scale Analysis Organic Molecules 89 Growth of Animal Cells in Culture 33 of Cell Proteins 65 Photosynthesis 90 Culture of Plant Cells 36 Identification of Cell Proteins 65