CE ESSENTIAL ES third edition S L CELL BIOLOGY E L N B T I OI A L L O G th ird e Y d itio n A l b e r t s B r a y H o p k i n J o h n s o n L e w i s R a f f R o b e r t s W a l t e r Alberts Bray Hopkin Johnson Lewis Raff Roberts Walter ISBN 978-0-8153-4130-7 9 780815 341307 ECB3 interactive DVD-ROM inside This page is intentionally left blank. ESSENTIAL third edition CELL BIOLOGY This page is intentionally left blank. ESSENTIAL third edition CELL BIOLOGY Alberts Bray Hopkin Johnson Lewis Raff Roberts walter Garland Science Essential Cell Biology Interactive Vice President: Denise Schanck Artistic and Scientifi c Direction: Peter Walter Senior Editor: Michael Morales Narrated by: Julie Theriot Production Editor and Layout: Emma Jeffcock Producer: Michael Morales Project Editor: Sigrid Masson Interface Design: Matthew McClements, Blink Studio Assistant Editor: Katherine Ghezzi Programming: Tom McElderry Editorial Assistant: Monica Toledo Text Editors: Eleanor Lawrence, Sherry Granum, Elizabeth Zayatz Copyeditor: Bruce Goatly Book and Cover Design: Matthew McClements, Blink Studio Illustrator: Nigel Orme Cover Illustration: Jose Ortega Indexer: Liza Furnival Permission Coordinator: Mary Dispenza Bruce Alberts received his Ph.D. from Harvard University and Julian Lewis received his D.Phil. from the University of is Professor of Biochemistry and Biophysics at the University Oxford and is a Principal Scientist at the London Research of California, San Francisco. He is the editor-in-chief of Science Institute of Cancer Research UK. magazine. For 12 years he served as President of the Martin Raff received his M.D. from McGill University and is U.S. National Academy of Sciences (1993-2005). at the Medical Research Council Laboratory for Molecular Dennis Bray received his Ph.D. from Massachusetts Institute Cell Biology and Cell Biology Unit and in the Biology of Technology and is currently an active emeritus professor at Department at University College London. University of Cambridge. In 2006 he was awarded the Microsoft Keith Roberts received his Ph.D. from the University of European Science Award. Cambridge and is Emeritus Fellow at the John Innes Centre, Karen Hopkin received her Ph.D. in biochemistry from the Norwich. Albert Einstein College of Medicine and is a science writer in Peter Walter received his Ph.D. from The Rockefeller Somerville, Massachusetts. University in New York and is Professor and Chairman Alexander Johnson received his Ph.D. from Harvard University of the Department of Biochemistry and Biophysics at the and is Professor of Microbiology and Immunology and Director University of California, San Francisco, and an Investigator of the Biochemistry, Cell Biology, Genetics, and Developmental of the Howard Hughes Medical Institute. Biology Graduate Program at the University of California, San Francisco. © 2010 by Bruce Alberts, Dennis Bray, Karen Hopkin, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter © 2004 by Bruce Alberts, Dennis Bray, Karen Hopkin, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter © 1998 by Bruce Alberts, Dennis Bray, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. All rights reserved. No part of this publication may be Library of Congress Cataloguing-in-Publication Data reproduced, stored in a retrieval system or transmitted in any form or by any means—electronic, mechanical, photocopying, Essential cell biology / Bruce Alberts ... [et al.]. -- 3rd ed. recording, or otherwise—without the prior written permission of p. cm. the copyright holder. ISBN 978-0-8153-4129-1 (hardcover) -- ISBN 978-0-8153- 4130-7 (pbk.) 1. Cytology. 2. Molecular biology. 3. Biochemistry. I. Published by Garland Science, Taylor & Francis Group, Alberts, Bruce. LLC, an informa business, 270 Madison Avenue, QH581.2.E78 2009 New York, NY 10016, USA, and 2 Park Square, Milton Park, 571.6--dc22 Abingdon, OX14 4RN, UK. 2009001400 Printed in the United States of America 15 14 13 12 11 10 9 8 7 6 5 4 3 2 Visit our website at http://www.garlandscience.com v Preface In our world there is no form of matter more astonishing than the living cell: tiny, fragile, marvelously intricate, continually made afresh, yet pre- serving in its DNA a record of information dating back more than three billion years, to a time when our planet had barely cooled from the hot materials of the nascent solar system. Ceaselessly re-engineered and diversified by evolution, extraordinarily versatile and adaptable, the cell still retains a core of complex self-replicating chemical machinery that is shared and endlessly repeated by every living organism on the face of the Earth, in every animal, every leaf, every bacterium in a piece of cheese, every yeast in a vat of wine. Curiosity, if nothing else, should drive us to study cell biology; but there are practical reasons, too, why cell biology should be a part of everyone’s education. We are made of cells, we feed on cells, and our world is made habitable by cells. We need to understand cell biology to understand our- selves; to look after our health; to take care of our food supplies; and to protect our endangered ecosystems. The challenge for scientists is to deepen knowledge and find new ways to apply it. But all of us, as citizens, need to know something of the subject to grapple with the modern world, from our own health affairs to the great public issues of environmental change, biomedical technologies, agriculture, and epidemic disease. Cell biology is a big subject, and it has links with almost every other branch of science. The study of cell biology therefore provides a great scientific education. However, it is easy to become lost in the detail and distracted by an overload of information and technical terminology. In this book we therefore focus on providing a digestible, straightforward, and engaging account of only the essential principles. We seek to explain, in a way that can be understood even by a reader approaching modern biology for the first time, how the living cell works: to show how the molecules of the cell—especially the protein, DNA, and RNA molecules—cooperate to cre- ate this remarkable system that feeds, responds to stimuli, moves, grows, divides, and duplicates itself. The need for a clear account of the essentials of cell biology became apparent to us while we were writing Molecular Biology of the Cell (MBoC), now in its fifth edition. MBoC is a large book aimed at advanced under- graduates and graduate students specializing in the life sciences or medicine. Many students and educated lay people who require an intro- ductory account of cell biology would find MBoC too detailed for their needs. Essential Cell Biology (ECB), in contrast, is designed to provide the fundamentals of cell biology that are required by anyone to understand both the biomedical and the broader biological issues that affect our lives. In this third edition, we have brought every part of the book up to date, with new material on chromosome structure and epigenetics, microRNAs vi Preface and RNAi, protein quality control, cell-cell recognition, genetic varia- tion, stem cells and their medical potential, rational cancer treatments, genome evolution, and many other topics. We have improved our discus- sion of energetics and thermodynamics, integrated the cell cycle and cell division into a single chapter, and updated the “How We Know” sections, describing experiments that illustrate how biologists tackle important questions and how their experimental results shape future ideas. As before, the diagrams in ECB emphasize central concepts and are stripped of unnecessary details. The key terms introduced in each chap- ter are highlighted when they first appear and are collected together at the end of the book in a large, illustrated glossary. We have not listed references for further reading: those wishing to explore a subject in greater depth are encouraged to consult the reading lists in MBoC5 or look for recent reviews in the current literature through one of the pow- erful search engines, such as Pubmed (http://www.ncbi.nlm.nih.gov) or Google Scholar (http://scholar.google.com). A central feature of the book is the many questions that are presented in the text margins and at the end of each chapter. These are designed to provoke students to think about what they have read and to encourage them to pause and test their understanding. Many questions challenge the student to place the newly acquired information in a broader biologi- cal context, and some have more than one valid answer. Others invite speculation. Answers to all the questions are given at the end of the book; in many cases these provide a commentary or an alternative perspective on material presented in the main text. For those who want to develop their active grasp of cell biology further and to get a deeper understanding of how cell biologists extract con- clusions from experiments, we recommend Molecular Biology of the Cell, Fifth Edition: A Problems Approach, by John Wilson and Tim Hunt. Though written as a companion to MBoC, this contains questions at all levels of difficulty and is a goldmine of thought-provoking problems for teachers and students. We have drawn upon it for some of the questions in ECB, and we are very grateful to its authors. The explosion of new imaging and computer technologies continues to give fresh and spectacular views of the inner workings of living cells. We have tried to capture some of the excitement of these advances in a revised and enlarged version of the Essential Cell Biology Interactive media player on the DVD-ROM included with each copy of the book. It contains over 130 video clips, animations, molecular structures, and high-resolu- tion micrographs—all designed to complement the material in individual book chapters. One cannot watch cells crawling, dividing, segregating their chromosomes, or rearranging their surface without a sense of won- der at the molecular mechanisms that underlie these processes. For a vivid sense of the marvel that science reveals beneath the surface of eve- ryday things, it is hard to match the movie of DNA replication included on the DVD. We hope that ECB Interactive will motivate and intrigue stu- dents while reinforcing basic concepts covered in the text, and thereby will make the learning of cell biology both easier and more rewarding. As with MBoC, each chapter of ECB is the product of communal effort, with individual drafts circulating from one author to another. In addition, many people have helped us, and these are credited in the Acknowledgments that follow. Despite our best efforts, it is inevitable that there will be errors in the book. We encourage readers who find them to let us know at [email protected], so that we can correct these errors in the next printing. vii Acknowledgments The authors acknowledge the many contributions of Siegfried, University of Pittsburgh at Johnstown; Roger professors and students from around the world in the D. Sloboda, Dartmouth College; Julio Soto, San Jose creation of this Third Edition. In particular, we are State University; Juliet Spencer, University of San grateful to the students who participated in the focus Francisco; Paul H. Tomasek, California State University groups; they provided invaluable feedback about their Northridge; Gary Wessel, Brown University; Esther experiences using the book and multimedia, and many F. Wheeler, Texas Tech University; Keren Witkin, of their suggestions were implemented in this edition. University of Massachusetts, Boston. We would also like to thank the professors who helped Special thanks go to David Morgan for his help in organize the focus groups at their schools: Chris formulating and reviewing the reorganized chapter on Brandl at University of Western Ontario, David L. Gard cell division. at University of Utah, Juliet Spencer at University of We are very grateful, too, to the readers who alerted us San Francisco, and Keren Witkin and Linda Huang to errors they had found in the previous edition. at University of Massachusetts, Boston. We greatly appreciate their hospitality. Many Garland staff contributed to the creation of this book and made our work on it a pleasure. First of all, We also received detailed reviews from instructors we owe a special debt to Michael Morales, our editor, using the second edition, and we would like to thank who coordinated the whole enterprise. He organized them for their work: Margarida D. Amaral, University the initial reviewing and the focus groups, worked of Lisbon; Lynne Arneson, American University; Karl closely with the authors on their chapters, urged us Aufderheide, Texas A&M University; David K. Banfield, on when we fell behind, and played a major part in The Hong Kong University of Science and Technology; the design, assembly, and production of Essential Cell Stephen F. Baron, Bridgewater College; Deborah Biology Interactive. Sigrid Masson managed the flow Bielser, University of Illinois at Urbana-Champaign; of chapters through the production process, proof- Barbara D. Boyan, Georgia Institute of Technology; read the entire book, and oversaw the writing of the Chris Brandl, University of Western Ontario; Keith accompanying question bank. Kate Ghezzi and Brown, University of Bristol; Jane Bruner, California Monica Toledo gave editorial assistance. Nigel Orme State University Stanislaus; Patrick Bryan, Middlesex took original drawings created by author Keith Roberts Community College; Sharon K. Bullock, Virginia and redrew them on a computer, or occasionally by Commonwealth University; Mike Clemens, St. George’s hand, with skill and flair. To Matt McClements goes Hospital Medical School, University of London; Anne the credit for the graphic design of the book and of Cordon, University of Toronto at Mississauga; Andrew the DVD. Emma Jeffcock did a brilliant job in laying Dalby, University of Exeter; Dan Eshel, Brooklyn out the whole book and meticulously incorporating College; Nicolas Forraz, Kingston University; David our endless corrections. Eleanor Lawrence and L. Gard, University of Utah; Mark Grimes, University Sherry Granum did the developmental editing of of Montana; Hollie Hale-Donze, Louisiana State individual chapters, repairing many rough edges, and University; Lynn Hannum, Colby College; Na’il M. Eleanor not only read the book from beginning to Hasan, Birzeit University; Jeannette M. Loutsch, end for clarity and consistency, but also revised and Arkansas State University; Charles Mallery, University extended the Glossary. Adam Sendroff and Lucy Brodie of Miami; Kathy Martin-Troy, Central Connecticut State gathered user feedback and launched the book into University; Gordon T.A. McEwan, Institute of Medical the wide world. Denise Schanck, the Vice President Sciences, University of Aberdeen; Colin McGuckin, of Garland Science, orchestrated all of this with great Kingston University; Gerard McNeil, York College, taste and diplomacy. We give our thanks to everyone The City University of New York; Roger W. Melvold, in this long list. University of North Dakota, School of Medicine & Health Sciences; Cristina Murga, Universidad Last but not least, we are grateful, yet again, to our Autónoma de Madrid; T. Page Owen, Jr., Connecticut families, our colleagues, and our childminders for their College; Martin Rumsby, University of York; Esther support and tolerance. viii Instructor and Student Resources Art of Essential Cell Biology, Third Edition Figure-Integrated Lecture Outlines The images from the book are available in two convenient The section headings, concept headings, and figures from formats: Powerpoint® and JPEG. They are located in fold- the text have been integrated into PowerPoint presenta- ers on the Media DVD-ROM that accompanies the book tions. These will be useful for instructors who would like or can be downloaded on the Web from Classwire™. On a head start creating lectures for their course. Like all of Classwire the individual JPEGs are searchable by figure our PowerPoint presentations, the lecture outlines can be number, figure name, or by keywords used in the figure customized. For example, the content of these presenta- legend from the book. tions can be combined with videos from the DVD-ROM and questions from the book or “Question Bank,” in order to create unique lectures that facilitate interactive learning in Media DVD-ROM the classroom. This resource is available on Classwire. Every copy of the book includes a DVD-ROM with the Question Bank following student and instructor resources: Written by Linda Huang, University of Massachusetts, Essential Cell Biology Interactive Boston, and Cheryl D. Vaughan, Harvard University Division This multimedia player contains over 130 movies (anima- of Continuing Education, the revised and expanded question tions, videos, and molecular tutorials), a self-test quiz for bank includes a variety of question formats: multiple- every chapter, and a cell explorer program that facilitates choice, fill-in-the-blank, true-false, matching, essay, and investigation of high-resolution micrographs. The mov- challenging “thought” questions. There are approximately ies are referenced directly in the textbook through movie 50-60 questions per chapter, and a large number of the “call outs” highlighted in red, for example (Movie 1.1). If multiple-choice questions will be suitable for use with per- you enter the movie number from the book into the movie- sonal response systems (i.e., clickers). The Question Bank locator window in the media player, the relevant movie will was created with the philosophy that a good exam should automatically appear. This feature, which was requested do much more than simply test students’ ability to memo- by students, should make it easier to integrate movies into rize information; it should require them to reflect upon and an active learning process. integrate information as a part of a sound understanding. It provides a comprehensive sampling of questions that can Student Self-Quizzes be used either directly or as inspiration for instructors to The quizzing feature, which is new to this edition, allows write their own test questions. Instructors can obtain the students to test themselves in basic reading comprehen- Question Bank by emailing: [email protected]. sion of each chapter. It is accessed through the Essential Cell Biology Interactive media player. Exploring the Living Cell DVD-Video Created by Christian Sardet, Centre National de la Recherche The Art of Essential Cell Biology, Third Edition Scientifique (CNRS), and directed by Véronique Kleiner, this This folder archive contains the figures from the book in unique DVD takes us on a journey through the basic unit JPEG and PowerPoint format as described above. of life: the cell. Using the earliest drawings and exciting imagery taken with today’s microscopes, renowned biolo- Movie Vault gists and young scientists explain their research and share This archive contains all of the movies from the Essential their discoveries. Learn how cells were discovered, how Cell Biology Interactive media player in three handy formats: they function, how they relate to health and disease, and WMV, QuickTime®, and iPod®. The WMV versions are suit- what the future holds. able for importing movies into PowerPoint for Windows®. The QuickTime versions are suitable for importing the Classwire™ movies into PowerPoint for the Macintosh®. And the iPod versions have been formatted specifically for iPod and The Classwire course management system, available at iTunes® use. www.classwire.com/garlandscience, allows instructors to build Websites for their courses easily. It also serves as an Media Guide online archive for instructor’s resources. After registering for This PDF overviews the contents of the DVD and contains Classwire, you will be able to download all the figures from the text of the voice-over narration for all of the movies. the book, as well as the movies from the DVD. Additional instructor’s resources for Garland Science textbooks are also available on Classwire. Please contact science@ garland.com for information on accessing the Classwire system. (Classwire™ is a trademark of Chalkfree, Inc.)