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22 GENETICS OF CANCER SOLUTIONS TO TEXT PROBLEMS 22.1 Progression of cells through the cell cycle is tightly regulated, and cancerous cells fail to respond to signals that normally regulate cellular proliferation. a. Which stages of the cell cycle are subject to regulation? b. What types of proteins regulate progression through the cell cycle, and what is the role of protein phosphorylation in this process? Answer: a. The cell cycle is regulated at cell cycle checkpoints that occur between G 1 and S (the START checkpoint in yeast), between G 2 and M, and during M just before the separation of chromatids. b. The cyclins and cyclin-dependent kinases (Cdks) regulate progression through the cell cycle. The levels of the cyclins oscillate in a regular pattern through the cell cycle. At each checkpoint, a cyclin binds to a Cdk to form a complex. When the cell is ready to pass the checkpoint, the complex is activated. For example, at the G 2 -M checkpoint, the cyclin-Cdk complex is activated by dephosphorylation of the Cdk. The activated Cdk then phosphorylates other cell cycle control proteins to affect their function, thereby leading to the cell’s transition into the next phase of the cell cycle. 22.2 Explain why HIV-1, the causative agent of AIDS, is considered a nononcogenic retrovirus, even though numerous types of cancers are frequently seen in patients with AIDS. Answer: HIV-1 is a retrovirus that infects and then kills cells of the immune system. This leads to a disabling of the immune response and an increase in susceptibility to certain types of cancer. In contrast to the mechanism by which cancer occurs following infection with HIV-1, an oncogenic retrovirus transforms the growth properties of infected cells to neoplastic growth. 22.3 Distinguish between a transducing retrovirus and a nontransducing retrovirus. Answer: Retroviruses are viruses that have two copies of an RNA genome within a protein core surrounded by a membranous envelope. Transducing retroviruses carry an oncogene from a host cell, while nontransducing retroviruses do not. Consequently, transducing retroviruses may be capable of transforming cells to a cancerous state. 22.4 Cellular proto-oncogenes and viral oncogenes are related in sequence, but they are not identical. What is the fundamental difference between the two?
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Answer: Cellular proto-oncogenes have important roles in regulating normal cellular processes such as cell division and differentiation. Viral oncogenes are mutated, abnormally expressed forms of proto- oncogenes that cause neoplastic growth. Viral oncogenes lack introns and, as shown in text Figure 22.7, p. 615, are often fused to viral genes. 22.5 An autopsy of a cat that died from feline sarcoma revealed neoplastic cells in the muscle and bone marrow but not in the brain, liver, or kidney. To gather evidence for the hypothesis that the virus FeSV contributed to the cancer, Southern blot analysis (see Chapter 16, pp. 439–441) was performed on DNA isolated from these tissues and on a cDNA clone of the FeSV viral genome. The DNA was digested with
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