1. What cellular mechanism(s) ensure that passage through the cell cycle is unidirectional and irreversible? What molecular machinery underlies these mechanism(s)?
2. What types of experimental strategies do researchers employ to study cell cycle progression? How do genetic and biochemical approaches to this topic differ?
3. Tim Hunt shared the 2001 Nobel Prize in Physiology or Medicine for his work in the discovery and characterization of cyclin proteins in eggs and embryos (see Classic Experiment 19-1). Describe the experimental steps that led him to his discovery of cyclins.
4. What experimental evidence indicates that cyclin B is required for a cell to enter mitosis? What evidence indicates that cyclin B must be destroyed for a cell to exit mitosis?
5. What physiological differences between S. pombe and S. cerevisiae make them useful yet complementary tools for studying the molecular mechanisms involved in cell cycle regulation and control?
6. In Xenopus, one of the substrates of mitotic CDKs is the phosphatase Cdc25. When phosphorylated by mitotic CDKs, Cdc25 is activated. What is the substrate of Cdc25? How does this information help to explain the rapid rise in mitotic CDK activity as cells enter mitosis?
7. Explain how CDK activity is modulated by the following proteins: (a) cyclin, (b) CAK, (c) Wee1, (d) p21.
8. Explain the role of CDK inhibitors. If cyclin-
9. Cancer cells typically lose cell cycle entry control. Explain how the following mutations, which are found in some cancer cells, lead to a bypass of these controls: (a) overexpression of cyclin D, (b) loss of Rb function, (c) loss of p16 function, (d) hyperactive E2F.
10. The Rb protein has been called the “master brake” of the cell cycle. Describe how the Rb protein acts as a cell cycle brake. How is the brake released in mid-
11. A common feature of cell cycle regulation is that the events of one phase ensure progression to a subsequent phase. In S. cerevisiae, G1 and G1/S phase CDKs promote S phase entry. Name two ways in which they promote the activation of S phase.
12. For S phase to be completed in a timely manner, DNA replication must be initiated from multiple origins in eukaryotes. In S. cerevisiae, what role do S phase CDKs and DDKs play to ensure that the entire genome is replicated once and only once per cell cycle?
13. In 2001, the Nobel Prize in Physiology or Medicine was awarded to three cell cycle scientists. Paul Nurse was recognized for his studies with the fission yeast S. pombe, in particular for the discovery and characterization of the wee1+ gene. What did the characterization of the wee1+ gene tell us about cell cycle control?
14. Describe how cells know whether sister kinetochores are properly attached to the mitotic spindle.
15. Describe the series of events by which APC/C promotes the separation of sister chromatids at anaphase.
16. Leland Hartwell, the third recipient of the 2001 Nobel Prize in Physiology or Medicine, was acknowledged for his characterization of cell cycle checkpoint pathways in the budding yeast S. cerevisiae. What is a cell cycle checkpoint pathway? When during the cell cycle do checkpoint pathways function? How do cell cycle checkpoint pathways help to preserve the genome?
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17. What role do tumor suppressors, including p53, play in mediating cell cycle arrest for cells with DNA damage?
18. Individuals with the hereditary disorder ataxia telangiectasia suffer from neurodegeneration, immunodeficiency, and an increased incidence of cancer. The genetic basis for ataxia telangiectasia is a loss-
19. Overall, meiosis and mitosis are analogous processes involving many of the same proteins. However, some proteins function uniquely in each of these cell-
20. Explain why the incidence of Down syndrome increases with maternal age.