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DNA Replication and Human Disease

(Cold Spring Harbor Monograph Series 47)

Book Series:  Cold Spring Harbor Monograph Series
Subject Area(s):  Molecular BiologyBiochemistry

Edited by Melvin L. DePamphilis, National Institutes of Health

Online Features: Website
A companion site which contains electronic versions of all figures from the book, along with complete versions of all chapters from our previous monograph on DNA Replication in Eukaryotic Cells

View sample pages from the book here

© 2006 • 814 pp., illus., appendices, index
Hardcover •
ISBN  978-087969766-2

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At least 5 trillion cell divisions are required for a fertilized egg to develop into an adult human, resulting in the production of more than 20 trillion meters of DNA! And yet, with only two exceptions, the genome is replicated once and only once each time a cell divides. How is this feat accomplished? What happens when errors occur? This book addresses these questions by presenting a thorough analysis of the molecular events that govern DNA replication in eukaryotic cells. The association between genome replication and cell proliferation, disease pathogenesis, and the development of targeted therapeutics is also addressed. At least 160 proteins are involved in replicating the human genome, and at least 40 diseases are caused by aberrant DNA replication, 35 by mutations in genes required for DNA replication or repair, 7 by mutations generated during mitochondrial DNA replication, and more than 40 by DNA viruses. Consequently, a growing number of therapeutic drugs are targeted to DNA replication proteins. This authoritative volume provides a rich source of information for researchers, physicians, and teachers, and will stimulate thinking about the relevance of DNA replication to human disease.


Chapter 1. Duplication of DNA in Eukaryotic Cells
Thomas J. Kelly and Bruce Stillman
Chapter 2. Eukaryotic DNA Replication Origins
Mirit I. Aladjem, Arturo Falasch, and David Kowalski
Chapter 3. Assembly of Pre–replication Complexes
Umasundari Sivaprasad, Anindya Dutta, and Stephen P. Bell
Chapter 4. Activation of Pre–replication Complexes
Johannes C. Walter & Hiroyuki Araki
Chapter 5. Eukaryotic DNA Replication Forks
Peter M.J. Burgers and Yeon–Soo Seo
Chapter 6. Chromatin Assembly
Paul D. Kaufman & Geneviève Almouzni
Chapter 7. Inheritance of Genomic Methylation Patterns
Robert A. Rollins, Marc Damelin, and Timothy H. Bestor
Chapter 8. Termination of DNA Replication
Deepak Bastia and Bidyut K. Mohanty
Chapter 9. DNA Replication and Nuclear Architecture
David M. Gilbert and Susan M. Gasser
Chapter 10. Temporal Order of DNA Replication
Anne D. Donaldson and Carl L. Schildkraut
Chapter 11. DNA Replication during Animal Development and Its Relevance to Gene Expression
Damien Grégoire and Marcel Méchali
Chapter 12. Developmental Gene Amplification
Brian R. Calvi
Chapter 13. Plant Cells and Viruses
Crisanto Gutierrez
Chapter 14. Archaeal, Bacterial, and Eukaryal DNA Replication Machines
Stephen D. Bell

Chapter 15. Regulating Initiation Events in Yeasts
Etienne Schwob and Karim Labib
Chapter 16. Regulating Initiation Events in Metazoa
Melvin L. DePamphilis and J. Julian Blow
Chapter 17. Responses to Aberrant DNA Replication and DNA Damage in Yeasts
Marco Foiani, Sanjay Kumar, and Joel A. Huberman
Chapter 18. Responses to Aberrant DNA Replication and DNA Damage in Metazoa
Jean Gautier and Jiri Bartek

Chapter 19. DNA Damage and Human Disease
Errol C. Friedberg
Chapter 20. DNA Polymerases and the Fidelity of DNA Replication
Polina V. Shcherbakova and Thomas A. Kunkel
Chapter 21. The Role of RF–C and PCNA Proteins in Maintaining Genomic Stability
Toshiki Tsurimoto
Chapter 22. DNA Helicases and Human Disease
Ashwini S. Kamath–Loeb, Michael Fry, and Lawrence A. Loeb
Chapter 23. DNA Replication, Repeat Instability, and Human Disease
John D. Cleary, Albert R. La Spada, and Christopher E. Pearson
Chapter 24. DNA Replication and Cancer
William C. Burhans, Antony M. Carr, and Geoffrey M. Wahl
Chapter 25. Cancer Diagnosis and DNA Replication
Nicholas Coleman, Anthony D. Mills, and Ronald A. Laskey
Chapter 26. Pharmacological Agents That Target DNA Replication
Yves Pommier and Robert B. Diasio
Chapter 27. Mitochondrial DNA Replication and Human Disease
David A. Clayton and Nils–Göran Larsson
Chapter 28. Telomere DNA Replication, Telomerase, and Human Disease
David C.F. Sealey, Virginia A. Zakian, and Lea Harrington

Chapter 29. Parvovirus
Susan F. Cotmore and Peter Tattersall
Chapter 30. Papillomavirus
Louise T. Chow and Thomas R. Broker
Chapter 31. Polyomavirus
Ellen Fanning and James M. Pipas
Chapter 32. Adenovirus
Peter C. van der Vliet and Rob C. Hoeben
Chapter 33. Herpes Simplex Virus
Sandra K. Weller and Donald M. Coen
Chapter 34. Epstein–Barr Virus
Wolfgang Hammerschmidt and Bill Sugden
Chapter 35. Poxvirus
Bernard Moss and Frank De Silva
Chapter 36. Hepadnavirus
Christoph Seeger and William S. Mason

A. Molecular Interaction Maps of DNA Replication
Mirit I. Aladjem and Kurt W. Kohn
B. The Evolutionary History of Proteins Involved in Pre–replication Complex Assembly
Lakshminarayan M. Iyer and L. Aravind

Table I. Size and Complexity of Eukaryotic Genomes
Table II. Names and Abbreviations for Organisms, Genes and Protein Complexes
Table III. Nomenclature for Proteins and Protein Complexes in Different Organisms
Table IVA. Phyletic Distribution of Proteins Involved in Pre–replication Complex Assembly
Table IVB. Alternative Names for Orthologs
Table V. Cellular Concentrations of Replication Origins and Pre–replication Complex Proteins
Table VI. Human Diseases Associated with Defects in DNA Replication and Repair
Table VII. Therapeutic Drugs That Target DNA Replication


review:  “...this book provides a broad and current synthesis of our understanding of genome duplication and it should be on the bookshelves of all students of DNA replication.”
      —Nature Cell Biology