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DNA Damage Checkpoints: The Emergency Brake on the Road to Cancer >> Content Detail



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Required Reading



SES #TOPICSREADINGS
1Introduction
2The cell cycle

Pines, J., and T. Hunter. "Isolation of a Human Cyclin cDNA: Evidence for Cyclin mRNA and Protein Regulation in the Cell Cycle and for Interaction with p34cdc2." Cell 58 (1989): 833-46.

Herrera, R. E., V. P. Sah, B. O. Williams, T. P. Mäkelä, R. A. Weinberg, and T. Jacks. "Altered Cell Cycle Kinetics, Gene Expression, and G1 Restriction Point Regulation in Rb-Deficient Fibroblasts." Molecular and Cellular Biology 16, no. 5 (1996): 2402-7.

3Cdk-regulation

Parker, L. L., and H. Piwnica-Worms. "Inactivation of the p34cdc2-Cyclin B Complex by the Human WEE1 Tyrosine Kinase." Science 257 (1992): 1955-1957.

Gautier, J., M. J. Solomon, R. N. Booher, J. F. Bazan, and M. W. Kirschner. "Cdc25 is a Specific Tyrosine Phosphatase that Directly Activates p34cdc2." Cell 67 (1991): 197-211.

4Checkpoint regulation of the cell cycle

Matsuoka, S., M. Huang, and S. J. Elledge. "Linkage of ATM to Cell Cycle Regulation by the Chk2 Protein Kinase." Science 282 (1998): 1893-7.

Brugarolas, J., C. Chandrasekaran, J. I. Gordon, D. Beach, T. Jacks, and G. J. Hannon. "Radiation-Induced Cell Cycle Arrest Compromised by p21 Deficiency." Nature 377 (1995): 552-7.

5p53 regulation

Hirao, A., Y. Y. Kong, S. Matsuoka, A. Wakeham, J. Ruland, H. Yoshida, D. Liu, S. J. Elledge, and T. W. Mak. "DNA Damage-Induced Activation of p53 by the Checkpoint Kinase Chk2." Science 287 (2000): 1824-7.

Honda, R., and Yasuda H. "Association of p19ARF with Mdm2 Inhibits Ubiquitin Ligase Activity of Mdm2 for Tumor Suppressor p53." The EMBO Journal 18 (1999): 22-27.

6The DNA damage checkpoint differs depending on cell cycle stage

Jazayeri, A., J. Falck, C. Lukas, J. Bartek, G. C. Smith, J. Lukas, and S. P. Jackson. "ATM- and Cell Cycle-Dependent Regulation of ATR in Response to DNA Double-Strand Breaks." Nature Cell Biology 8 (2006): 37-45.

Jin, J., J. Shirogane, L. Xu, G. Nalepa, J. Qin, S. J. Elledge, and J. W. Harper. "SCFb-TRCP Links Chk1 Signaling to Degradation of the Cdc25A Protein Phosphatase." Genes & Development 17 (2003): 3062-3074.

7'To die or not to die' - the decision between repair and apoptosis

Yu, J., L. Zhang, P. M. Hwang, K. W. Kinzler, and B. Vogelstein. "PUMA Induces the Rapid Apoptosis of Colorectal Cancer Cells." Molecular Cell 7 (2001): 673-82.

Adimoolam, S., and J. M. Ford. "p53 and DNA Damage-inducible Expression of the Xeroderma Pigmentosum Group C Gene." Proc Natl Acad Sci USA 99 (2002): 12985-90.

8Structural insights into the DNA damage response

Moreno-Herrero, F., M. de Jager, N. H. Dekker, R. Kanaar, C. Wyman, and C. Dekker. "Mesoscale Conformational Changes in the DNA-Repair Complex Rad50/Mre11/Nbs1 upon Binding DNA." Nature 437 (2005): 440-3.

Stucki, M., J. A. Clapperton, D. Mohammad, M. B. Yaffe, S. J. Smerdon, and S. P. Jackson. "MDC1 Directly Binds Phosphorylated Histone H2AX to Regulate Cellular Responses to DNA Double-Strand Breaks." Cell 123 (2005): 1213-26.

9Field trip: Visit to an MIT Biology laboratory
10Defective DNA damage responses and cancer

Lam, M. H., Q. Liu, S. J. Elledge, and J. M. Rosen. "Chk1 is Haploinsufficient for Multiple Functions Critical to Tumor Suppression." Cancer Cell 6 (2004): 45-59.

Ventura, A., D. G. Kirsch, M. E. McLaughlin, D. A. Tuveson, J. Grimm, L. Lintault, J. Newman, E. E. Reczek, R. Weissleder, and T. Jacks. "Restoration of p53 Function Leads to Tumour Regression In vivo." Nature 445 (2007): 661-5.

11Checkpoint-related syndromes

Gilad, S., L. Chessa, R. Khosravi, P. Russell, Y. Galanty, M. Piane, R. A. Gatti, T. J. Jorgensen, Y. Shiloh, and A. Bar-Shira. "Genotype-Phenotype Relationships in Ataxia-Telangiectasia and Variants." American Journal of Human Genetics 62 (1998): 551-61.

Bell, D. W., J. M. Varley, T. E. Szydlo, D. H. Kang, D. C. Wahrer, K. E. Shannon, M. Lubratovich, S. J. Verselis, K. J. Isselbacher, J. F. Fraumeni, J. M. Birch, F. P. Li, J. E. Garber, and D. A. Haber. "Heterozygous Germ Line hCHK2 Mutations in Li-Fraumeni Syndrome." Science 286 (1999): 2528-31.

12Treatment of disease based upon knowledge about the DNA damage response

Farmer, H., N. McCabe, C. J. Lord, A. N. Tutt, D. A. Johnson, T. B. Richardson, M. Santarosa, K. J. Dillon, I. Hickson, C. Knights, N. M. Martin, S. P. Jackson, G. C. Smith, and A. Ashworth. "Targeting the DNA Repair Defect in BRCA Mutant Cells as a Therapeutic Strategy." Nature 434 (2005): 917-21.

Vassilev, L. T., B. T. Vu, B. Graves, D. Carvajal, F. Podlaski, Z. Filipovic, N. Kong, U. Kammlott, C. Lukacs, C. Klein, N. Fotouhi, and E. A. Liu EA. "In vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2." Science 303 (2004): 844-8.

13Final presentations



Suggested Reading


Kastan, M. B., and J. Bartek. "Cell-cycle Checkpoints and Cancer." Nature 432 (2004): 316-323.

Kastan, M. B., and D. Lim. "The Many Substrates and Functions of ATM." Nature Reviews: Molecular Cell Biology 1 (2000): 179-186.

Kawabe, T. "G2 Checkpoint Abrogators as Anticancer Drugs." Molecular Cancer Therapeutics 3 (2004): 513-519.

Shiloh, Y. "ATM and Related Protein Kinases: Safeguarding Genome Integrity." Nature Reviews: Cancer 3 (2003): 155-168.

Zhou, B. S., and J. Bartek. "Targeting the Checkpoint Kinases: Chemosensitization Versus Chemoprotection." Nature Reviews: Cancer 4 (2004): 1-10.

Zhou, B. S., and S. J. Elledge. "The DNA Damage Response: Putting Checkpoints in Perspective." Nature 408 (2000): 433-439.


 








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