The DNA Damage Response: Implications on Cancer Formation and Treatment

Transcription

1 The DNA Damage Response: Implications on Cancer Formation and Treatment

2 Kum Kum Khanna Yosef Shiloh Editors The DNA Damage Response: Implications on Cancer Formation and Treatment 123

3 Editors Dr. Kum Kum Khanna Queensland Institute of Medical Research Signal Transduction Laboratory 300 Herston Road Herston QLD 4006 Australia Dr. Yosef Shiloh Tel Aviv University Sackler School of Medicine Dept. Human Molecular Genetics & Biochemistry Tel Aviv Ramat Aviv Israel ISBN e-isbn DOI / Springer Dordrecht Heidelberg London New York Library of Congress Control Number: Springer Science+Business Media B.V No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Printed on acid-free paper Springer is part of Springer Science+Business Media (

4 Preface The field of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the maintenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated system designated the DNA damage response. This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, transcriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to specific damaging agents, immunodeficiency, genomic instability, cancer predisposition and premature aging. The finding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving field, and the advances in our understanding of the complex network of processes that respond to DNA damage. The researchers who contributed chapters have profound knowledge of the recent advances in DNA damage signalling and repair and their implications for carcinogenesis, and are well positioned to anticipate upcoming developments in their respective fields. The book is divided into chapters that deal with the elaborate surveillance system and repair mechanisms used by cells to suppress mutagenic lesions to avoid cancer. It provides snapshots of what is known to date about DNA damage signalling, cell cycle checkpoints, some of the major DNA repair pathways, functional links between DNA damage, genomic instability and cancer, and how this knowledge can be mined for the new treatment modalities for cancer. Where major players in this response are potential targets for cancer therapy, the developments are discussed. We hope the book will provide the reader with a framework to understand current concepts in DNA damage signaling and repair, their critical role in the maintenance of genomic stability, how the dysfunction of v

5 vi Preface these mechanisms contributes to tumorigenesis, and how those mechanisms can be exploited for therapeutic gains. We thank all the authors who made this book possible. Their timely contributions bring us up to date on this crucial area of research on the close link between genome instability and cancer. Australia Israel Kum Kum Khanna Yosef Shiloh

6 Contents 1 DNA Damage Sensing and Signaling... 1 Daniel Durocher 2 Signaling at Stalled Replication Forks Daniel A. Mordes and David Cortez 3 An Oncogene-Induced DNA Replication Stress Model for Cancer Development Thanos D. Halazonetis 4 Cellular Responses to Oxidative Stress Inbal Dar and Ari Barzilai 5 Cell Cycle Regulation and DNA Damage Ryo Sakasai and Randal S. Tibbetts 6 Chromatin Modifications Involved in the DNA Damage Response to Double Strand Breaks Julia Pagan, Emma Bolderson, Mathew Jones, and Kum Kum Khanna 7 Telomere Metabolism and DNA Damage Response Tej K. Pandita 8 DNA Double Strand Break Repair: Mechanisms and Therapeutic Potential Laura M. Williamson, Chris T. Williamson, and Susan P. Lees-Miller 9 DNA Base Excision Repair: A Recipe for Survival Rabindra Roy and Sankar Mitra 10 DNA Damage Tolerance and Translesion Synthesis Alan R. Lehmann 11 Nucleotide Excision Repair: from DNA Damage Processing to Human Disease Mischa G. Vrouwe and Leon H.F. Mullenders vii

7 viii Contents 12 Chromosomal Single-Strand Break Repair Keith W. Caldecott 13 Mouse Models of DNA Double Strand Break Repair Deficiency and Cancer Sachin Katyal and Peter J. McKinnon 14 Cancer Biomarkers Associated with Damage Response Genes Anne E. Kiltie, Marie Fernet, and Janet Hall 15 Linking Human RecQ Helicases to DNA Damage Response and Aging Wen-Hsing Cheng, Byungchan Ahn, and Vilhelm A. Bohr 16 Single-Stranded DNA Binding Proteins Involved in Genome Maintenance Derek J. Richard and Kum Kum Khanna 17 The Fanconi anemia-brca Pathway and Cancer Toshiyasu Taniguchi 18 BRCA1 and BRCA2: Role in the DNA Damage Response, Cancer Formation and Treatment Kienan Savage and D. Paul Harkin Index

8 Contributors Byungchan Ahn Department of Life Sciences, University of Ulsan, Ulsan , Korea, Ari Barzilai Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Vilhelm A. Bohr Laboratory of Molecular Gerontology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA, Emma Bolderson Signal Transduction Laboratory, The Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia, Keith W. Caldecott Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, BN1 9RQ, UK, Wen-Hsing Cheng Department of Nutrition and Food Science, University of Maryland, College Park, MD, 20742, USA, David Cortez Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA, Inbal Dar Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel, Daniel Durocher Samuel Lunenfeld Research Institute, Centre for Systems Biology, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada M5G 1X5, Marie Fernet INSERM U612, Bats , Centre Universitaire, Orsay, 91405, France; Institut Curie-Recherche, Bats , Centre Universitaire, Orsay, France, Thanos D. Halazonetis Department of Molecular Biology and Department of Biochemistry, University of Geneva, CH-1205, Geneva, Switzerland, Janet Hall INSERM U612, Bats , Centre Universitaire, Orsay, 91405, France; Institut Curie-Recherche, Bats , Centre Universitaire, Orsay, France, ix

9 x Contributors D. Paul Harkin Centre for Cancer Research and Cell Biology, Queen s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK, d.harkin@qub.ac.uk Mathew Jones Signal Transduction Laboratory, The Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia, mathew.jones@qimr.edu.au Sachin Katyal Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA, sachin.katyal@stjude.org Kum Kum Khanna Cancer and Cell Biology Division, Signal Transduction Laboratory, The Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia, kumkum.khanna@qimr.edu.au Anne E Kiltie Section of Experimental Oncology, Leeds Institute of Molecular Medicine, St James s University Hospital, Leeds LS9 7TF, UK, a.e.kiltie@leeds.ac.uk Susan P. Lees-Miller Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada, leesmill@ucalgary.ca Alan R Lehmann Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, UK, a.r.lehmann@sussex.ac.uk Peter J. McKinnon Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA, peter.mckinnon@stjude.org Sankar Mitra Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX , USA, samitra@utmb.edu Daniel A. Mordes Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA, daniel.mordes@vanderbilt.edu Leon H.F. Mullenders Department of Toxicogenetics, Leiden University Medical Center, Leiden, Nederland, l.mullenders@lumc.nl Julia Pagan Signal Transduction Laboratory, The Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia, julia.pagan@qimr.edu.au Tej K. Pandita Department of Radiation Oncology, Washington University School of Medicine, 4511 Forest Park Ave., St Louis, MO 63108, USA, pandita@wustl.edu Derek J Richard Cancer and Cell Biology Division, The Queensland Institute of Medical Research, 300 Herston Road, Herston Qld 4006, Australia, derek.richard@qimr.edu.au Rabindra Roy Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC , USA, rr228@georgetown.edu

10 Contributors xi Ryo Sakasai Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA, Kienan Savage Centre for Cancer Research and Cell Biology, Queen s University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, UK, k.savage@qub.ac.uk Toshiyasu Taniguchi Divisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., C1-015, Seattle, WA , USA, ttaniguc@fhcrc.org Randal S. Tibbetts Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA, rstibbetts@wisc.edu Mischa G. Vrouwe Department of Toxicogenetics, Leiden University Medical Center, Leiden, Nederland Laura M. Williamson Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB T2N 4N1, Canada, lbaxter@ucalgary.ca Chris T. Williamson Department of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, 3330 Hospital Drive, NW, Calgary, AB T2N 4N1, Canada, ctwillia@ucalgary.ca