The DNA Damage Response: Implications on Cancer Formation and Treatment

1. Front Matter

   Pages i-xi

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2. DNA Damage Sensing and Signaling

   • Daniel Durocher

   Pages 1-24

3. Signaling at Stalled Replication Forks

   • Daniel A. Mordes, David Cortez

   Pages 25-45

4. An Oncogene-Induced DNA Replication Stress Model for Cancer Development

   • Thanos D. Halazonetis

   Pages 47-63

5. Cellular Responses to Oxidative Stress

   • Inbal Dar, Ari Barzilai

   Pages 65-79

6. Cell Cycle Regulation and DNA Damage

   • Ryo Sakasai, Randal S. Tibbetts

   Pages 81-107

7. Chromatin Modifications Involved in the DNA Damage Response to Double Strand Breaks

   • Julia Pagan, Emma Bolderson, Mathew Jones, Kum Kum Khanna

   Pages 109-131

8. Telomere Metabolism and DNA Damage Response

   • Tej K. Pandita

   Pages 133-156

9. DNA Double Strand Break Repair: Mechanisms and Therapeutic Potential

   • Laura M. Williamson, Chris T. Williamson, Susan P. Lees-Miller

   Pages 157-177

10. DNA Base Excision Repair: A Recipe for Survival

    • Rabindra Roy, Sankar Mitra

    Pages 179-208

11. DNA Damage Tolerance and Translesion Synthesis

    • Alan R. Lehmann

    Pages 209-234

12. Nucleotide Excision Repair: from DNA Damage Processing to Human Disease

    • Mischa G. Vrouwe, Leon H.F. Mullenders

    Pages 235-259

13. Chromosomal Single-Strand Break Repair

    • Keith W. Caldecott

    Pages 261-284

14. Mouse Models of DNA Double Strand Break Repair Deficiency and Cancer

    • Sachin Katyal, Peter J. McKinnon

    Pages 285-305

15. Cancer Biomarkers Associated with Damage Response Genes

    • Anne E. Kiltie, Marie Fernet, Janet Hall

    Pages 307-330

16. Linking Human RecQ Helicases to DNA Damage Response and Aging

    • Wen-Hsing Cheng, Byungchan Ahn, Vilhelm A. Bohr

    Pages 331-347

17. Single-Stranded DNA Binding Proteins Involved in Genome Maintenance

    • Derek J. Richard, Kum Kum Khanna

    Pages 349-366

18. The Fanconi anemia-BRCA Pathway and Cancer

    • Toshiyasu Taniguchi

    Pages 367-414

19. BRCA1 and BRCA2: Role in the DNA Damage Response, Cancer Formation and Treatment

    • Kienan Savage, D. Paul Harkin

    Pages 415-443

20. Back Matter

    Pages 445-449

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The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem 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, tr- scriptional 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 speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding 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 ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

• BRCA
• Chromosom
• DNA
• DNA Damage
• Telomere
• aging
• genes

• Signal Transduction Laboratory, Queensland Institute of Medical Research, Herston, Australia

  Kum Kum Khanna

• Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

  Yosef Shiloh

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