© 2006 • 814 pp., illus., appendices, index
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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.

  “...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

PART I: CELLULAR DNA REPLICATION

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

PART II: REGULATION OF DNA REPLICATION AND CELL PROLIFERATION

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

PART III: CELLULAR DNA REPLICATION AND HUMAN DISEASE

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

PART IV: VIRAL DNA REPLICATION AND HUMAN DISEASE

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

APPENDIX 1

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

APPENDIX 2

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