A “cell-cycle engine” that functions in all eukaryotic organisms was defined. This mechanism consists of cyclin-regulated cell-cycle kinases that provide the crucial checkpoints and feedback controls that regulate cell division. This chapter utilizes T cells to illustrate the transition steps that regulate cell-cycle entry, progression, and exit. The kinases and phosphatases that carry out this phase of cyclin-dependent kinase regulation provide additional links between environmental signals and activation of the cell-cycle machinery. The S-phase checkpoint relies on detection of stalled replication or DNA damage. The S-phase checkpoint is fallible, so a partially redundant checkpoint exists during the G2 phase. Cancer is a condition where cells divide uncontrollably, making it easy to see how it can be linked to abnormal cell-cycle function. The gross abnormalities are prognostic, but even subtle quantitative differences in cyclin expression, Rb and phosphorylation, can influence tumor progression and serve as useful indicators of prognosis for hematopoietic tumors.
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