DNA Topoisomerases and Cancer
DNA topoisomerases are present in all living organisms and are essential to maintaining the helical structure of DNA. They are highly relevant for cancer because a number of anti-cancer drugs selectively target two of the human enzymes, DNA topoisomerases
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Yves Pommier Editor
DNA Topoisomerases and Cancer
Editor Yves Pommier Laboratory of Molecular Pharmacology Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD, USA [email protected]
ISBN 978-1-4614-0322-7 e-ISBN 978-1-4614-0323-4 DOI 10.1007/978-1-4614-0323-4 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011937449 Springer Science+Business Media, LLC 2012 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com)
Preface
This book brings together a unique collection of chapters that provide detailed information on human topoisomerases. It covers current knowledge on human DNA topoisomerases, their targeting by anticancer drugs and carcinogenic lesions, the clinical use of topoisomerase inhibitors and the various pathways and cellular responses involved in the repair of topoisomerase-mediated DNA damage. Contributors to this book are world class scientists who have made key discoveries in the field. I wish to thank them for their time, enthusiasm and for making this book a collection of complementary articles covering the topoisomerase field both from basic biology and therapeutic viewpoints. I dedicate this book to Dr. Kurt W. Kohn who in 1979 suggested that a topoisomerase should be the target of anticancer drugs. Kurt Kohn inspired me to work on DNA topoisomerases starting in 1981 and has remained a precious collaborator ever since. Bethesda, MD
Yves Pommier
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Contents
1
Introduction and Historical Perspective .............................................. Patrick Forterre
2
Human DNA Topoisomerase I: Structure, Enzymology and Biology ..................................................... James J. Champoux
1
53
3
Mitochondrial Topoisomerases ............................................................. Ilaria Dalla Rosa, Yves Pommier, and Hongliang Zhang
4
Structure and Mechanism of Eukaryotic Type IIA Topoisomerases....................................................................................... James M. Berger and Neil Osheroff
87
Essential Functions of Topoisomerase IIIa in the Nucleus and Mitochondria..........................................................................
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