Review The Concepts

1. What strategy ensures that passage through the cell cycle is unidirectional and irreversible? What is the molecular machinery that underlies this strategy?

2. When fused with an S-phase cell, cells in which of the following phases of the cell cycle will initiate DNA replication prematurely—G1? G2? M? Predict the effect of fusing a cell in G1 and a cell in G2 with respect to the timing of S phase in each cell.

3. In 2001, the Nobel Prize in Physiology or Medicine was awarded to three cell cycle scientists. Sir Paul Nurse was recognized for his studies with the fission yeast ,S. pombe, in particular for the discovery and characterization of the weel gene. What is the wee phenotype? What did the characterization of the wee1 gene tell us about cell cycle control?

4. Tim Hunt shared the 2001 Nobel Prize for his work in the discovery and characterization of cyclin proteins in eggs and embryos. 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. Leeland Hartwell, the third recipient of the 2001 Nobel Prize, was acknowledged for his characterization of cell cycle checkpoints in the budding yeast S. cerevisiae. What is a cell cycle checkpoint? Where do checkpoints occur in the cell cycle? How do cell cycle checkpoints help to preserve the fidelity of the genome?

6. In Xenopus, one of the substrates of MPF is the Cdc25 phosphatase. When phosphorylated by MPF, Cdc25 is activated. What is the substrate of Cdc25? How does this information explain the autocatalytic nature of MPF as described in Figure 21-6?

7. Explain how CDK activity is modulated by the following proteins: (a) cyclin, (b) CAK, (c) Wee1, (d) p21.

8. Three known substrates of MPF or kinases regulated by MPF are the nuclear lamins, subunits of condensin, and myosin light chain. Describe how the phosphorylation of each of these proteins affects its function and progression through mitosis.

9. Describe the series of events by which the APC promotes the separation of sister chromatids at anaphase.

10. A common feature of cell cycle regulation is that the events of one phase ensure progression into a subsequent phase. In ,S. cerevisiae, Cdc28-Clns catalyze progression through G1, and Cdc28-Clbs catalyze progression through S/G2/M. Name three ways in which the activity of Cdc28-Clns promotes the activation of Cdc28-Clbs.

11. For S phase to be completed in a timely manner, DNA replication initiates from multiple origins in eukaryotes. In sS. cerevisiae, what role do S-phase CDK-cyclin complexes play to ensure that the entire genome is replicated once and only once per cell cycle?

12. What is the functional definition of the restriction point? Cancer cells typically lose restriction point controls. Explain how the following mutations, which are found in some cancer cells, lead to a bypass of restriction point controls:

(a) overexpression of cyclin D, (b) loss of Rb function, (c) infection by retroviruses encoding v-Fos and v-Jun.

13. Individuals with the hereditary disorder ataxia telan-giectasia suffer from neurodegeneration, immunodeficiency, and increased incidence of cancer. The genetic basis for ataxia telangiectasia is a loss-of-function mutation in the ATM gene (ATM = ataxia telangiectasia-mutated). Name two substrates of ATM. How does the phosphorylation of these substrates lead to inactivation of CDKs to enforce cell cycle arrest at a checkpoint?

14. Meiosis and mitosis are overall analogous processes involving many of the same proteins. However, some proteins function uniquely in each of these cell division events. Explain the meiosis-specific function of the following: (a) Ime2,

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