| WEEK # | TOPICS | READINGS |
|---|---|---|
| 1 |
Introduction & Overview | No Readings |
| 2 |
Alkylating agents: How chemical warfare became medicine |
Krumbhaar, E. B., and H. D. Krumbhaar. "The Blood and Bone Marrow in Yellow Cross Gas (Mustard Gas) Poisoning. Changes Produced in the Bone Marrow of Fatal Cases." Journal of Medical Research 40, no. 3 (1919): 497–508. Windtrobe, M. M., and C. M. Huguley. "Nitrogen–Mustard Therapy for Hodgkin's Disease, Lymphosarcoma, the Leukemias, and Other Disorders." Cancer 1, no. 3 (1948): 357–82. |
| 3 |
Direct Repair: Levels of O6–methylguanine–DNA methyltransferase (MGMT) as a potential predictor of response to alkylation–based chemotherapeutics |
Glassner, Brian J., Geert Weeda, et al. "DNA Repair Methyltransferase (Mgmt) Knockout Mice are Sensitive to the Lethal Effects of Chemotherapeutic Alkylating Agents." Mutagenesis 14, no. 3 (1999): 339–47. Kitange, Gaspar J., Brett L. Carlson, et al. "Induction of MGMT Expression is Associated with Temozolomide Resistance in Glioblastoma Xenografts." Neuro-Oncology 11, no. 3 (2009): 281–91. |
| 4 |
Mismatch Repair: A guardian against replication errors |
Prolla, T. A., Q. Pang, et al. "MLH1, PMS1, and MSH2 Interactions During the Initiation of DNA Mismatch Repair in Yeast." Science 265, no. 5175 (1994): 1091–3. Stojic, Lovorka, Nina Mojas, et al. "Mismatch Repair–Dependent G2 Checkpoint Induced by Low Doses of SN1 Type Methylating Agents Requires the ATR Kinase." Genes & Development 18, no. 11 (2004): 1331–44. |
| 5 |
Mutations and Epigenetics: Multiple means by which inactivation of the mismatch repair pathway complicates the treatment of cancer |
Nyström-Lahti, Minna, Paula Kristo, et al. "Founding Mutations and Alu–Mediated Recombination in Hereditary Colon Cancer." Nature Medicine 1, no. 11 (1995): 1203–6. Li, Feng, Guogen Mao, et al. "The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair through its Interaction with MutSα." Cell 153, no. 3 (2013): 590–600. |
| 6 |
Base Excision Repair: Intermediate threat to genomic stability |
Calvo, Jennifer A., Catherine A. Moroski-Erkul, et al. "Aag DNA Glycosylase Promotes Alkylation–Induced Tissue Damage Mediated by Parp1." Public Library of Science Genetics 9, no. 4 (2013): 1–13. Lauritzen, Knut H., Olve Moldestad, et al. "Mitochondrial DNA Toxicity in Forebrain Neurons Causes Apoptosis, Neurodegeneration, and Impaired Behavior." Molecular and Cellular Biology 30, no. 6 (2010): 1357–67. |
| 7 |
Base Excision Repair: The GO system limits mutagenesis by oxidative damage |
Ruggieri, V, E. Pin, et al. "Loss of MUTYH Function in Human Cells Leads To Accumulation of Oxidative Damage and Genetic Instability." Oncogene 32, no. 2 (2013): 1–9. Oka, Sugako, Mizuki Ohno, et al. "Two Distinct Pathways of Cell Death Triggered By Oxidative Damage To Nuclear and Mitochondrial DNAs." The Embo Journal 27, no. 2 (2008): 421–32. |
| 8 |
Field Trip to Blueprint Medicines | No Readings |
| 9 |
16,568 base pairs: Mitochondrial DNA repair mechanisms and the deadly consequences of failing to maintain the mitochondrial genome |
Furda, Amy M., Adele M. Marrangoni, et al. "Oxidants and Not Alkylating Agents Induce Rapid MTDNA Loss and Mitochondrial Dysfunction." DNA Repair 11, no. 8 (2012): 684–92. Chan, Sherine S. L., Matthew J. Longley, et al. "The Common A467T Mutation in the Human Mitochondrial DNA Polymerase (POLG) Compromises Catalytic Efficiency and Interaction With the Accessory Subunit." The Journal of Biological Chemistry 280, no. 36 (2005): 31341–6. |
| 10 |
Extreme sun–sensitivity: Nucleotide excision repair defects in xeroderma pigmentosum patients |
Mu, David, David S. Hsu, et al. "Reaction Mechanism of Human DNA Repair Excision Nuclease." The Journal of Biological Chemistry 271, no. 14 (1996): 8285–94. Li, Chunying, Ming Yin, et al. "Polymorphisms of Nucleotide Excision Repair Genes Predict Melanoma Survival." Journal of Investigative Dermatology 133, no. 7 (2013): 1813–21. |
| 11 |
Unwinding less: Depletion of Werner helicase activity as both a cause and a treatment of disease |
Kanagaraj, Radhakrishnan, Prasanna Parasuraman, et al. "Involvement of Werner Syndrome Protein in MUTYH–Mediated Repair of Oxidative DNA Damage." Nucleic Acids Research 40, no. 17 (2012): 8449–59. Aggarwal, Monika, Joshua A. Sommers, et al. "Inhibition of Helicase Activity By a Small Molecule Impairs Werner Syndrome Helicase (WRN) Function in the Cellular Response to DNA Damage or Replication Stress." Proceedings of the National Academy of Sciences of the United States of America 108, no. 4 (2011): 1525–30. |
| 12 |
Stem cells: DNA damage and differentiation, do they mix? |
Luo, Li Z., Sailesh Gopalakrishna–Pillai, et al. "DNA Repair in Human Pluripotent Stem Cells is Distinct From That in Non–Pluripotent Human Cells." Public Library of Science One 7, no. 3 (2012): 1–16. Guo, F., J. Li, et al. "MTOR Regulates DNA Damage Response through NF–κB–Mediated FANCD2 Pathway in Hematopoietic Cells." Leukemia 27 (2013): 2040–6. |
| 13 |
Students Oral Presentation Assignments | No Readings |