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Set 7 - Problem Set 7 Bi9 Cell Biology Spring 2011...

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Unformatted text preview: Problem Set 7 Bi9 Cell Biology Spring 2011 Instructions: • There are 3 Parts. • Type your answers. • Print and turn in 3 separate sheets. 1 sheet for each part. All answers for each part should not fill more than one page. • You do not have to staple the sheets together, since you will... • Write your FULL NAME on every page. • Problem Set 7 is due on Tuesday May 24th at 5 pm. A box will be available on the first floor of Broad to turn in your work. • Be sure to cite any sources you use besides Molecular Biology of the Cell. If you use websites, include link and date accessed. Part I A. (5 points) Briefly list the different reasons for undergoing apoptosis. B. (5 points) Discuss the main differences between apoptosis and necrosis. (less than 8 lines) C. (5 points) Explain the main role of caspases in apoptosis. Make sure you comment on the residue they act on and the kind of reactions they catalyze. DNA fragmentation is a biochemical hallmark of apoptosis. It happens because of caspase ­activated DNases (CAD), which, as their name implies, cleave DNA and are activated by caspases. CAD exists in a normal cell as a complex with its inhibitor ICAD. In an apoptotic cell ICAD is caspase ­cleaved, which dissociates the complex and allows cleavage of chromosomal DNA by CAD. You are studying transgenic mice, which have a mutation on an ICAD that makes ICAD resistant to caspase activity. You also have the wild type mice. By treatment with anti ­Fas antibody for 3 hours you can induce apoptosis in isolated mouse thymocytes. You can later purify the DNA and analyzed it by electrophoresis on an agarose gel. D.(5 points) What type of apoptosis is caused by anti ­Fas? How do caspases get activated in this case? (In less than 5 lines) E.(5 points) Sketch agarose gels for wildtype and transgenic mice induced with anti ­Fas. Be sure to include negative controls in your gel. Part II A. (5 points) In order to survive and proliferate, malignant cells need certain requirements. Blood supply is one of them. Briefly describe this process through which the tumor cells obtain that supply and its importance in terms of tumor’s survival. B. (5 points) Explain why p53 is a tumor suppressor gene. Discuss the consequences of a mutation that inactivates p53? C. (5 points) Suggest two sites on p53 that could be mutated to promote cell proliferation. D. (5 points) Explain what histone deacetylases do and why they have become popular targets of cancer drug therapies. What type of control to they exert on the cell? Part III A.(5 points) Cancer cells show defects in the normal cell division and differentiation. What are the main altered processes involved in tumorigenesis related to the previously mentioned processes? Below is a figure from a paper which reports on the role of Cyclin D in a mouse model of breast cancer. In their investigation, the authors looked at the tumorgenesis of different oncogenes: myc, Wnt, ras, and neu. They crossed mice expressing high levels of each of these genes with mice containing (D1 +/+) or lacking cyclin D1 (D1 ­/ ­). B. (5 points) Which oncogene(s) require cyclin D1 to cause tumor growth? How can you tell? Be sure to discuss all the genes above. C. (5 points) Based on these data, if you had to choose one of the five genes to target with a drug, which would you choose? How would you screen cancers for your new therapy? ...
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