4 Cell Cycle Control, Checkpoints, and Stem Cell Biology

Abstract

During the past decade, we have seen remarkable advances in our understanding of how the eukaryotic cell cycle is regulated. As a result, we now have a detailed molecular description of the cell cycle machinery that controls both the G₁/S and G₂/M-phase transitions. Moreover, we have also seen the discovery of checkpoint controls that delay the cell cycle in response to intracellular perturbations including DNA damage, incomplete DNA replication, or a defective mitotic spindle. These allow time for repairs to be completed prior to chromosome segregation and cell division. Finally, the cell cycle can be regulated in response to extracellular signals generated by changes in nutrient status, pheromones, and mitogens.

Although we have made significant progress in our understanding of how the cell cycle is controlled in a variety of different organisms, little has been established on how the cell cycle is regulated in stem cells. Stem cells have an unlimited capacity for both self-renewal and production of differentiated progeny, and both processes must be tightly regulated to ensure the survival of the organism. Although it is still not clear what controls the decision to either self-renew or differentiate, or how the fate of a differentiating daughter cell is determined, the regulation of the cell cycle appears to play a key role in these processes. In this chapter, we provide a general overview of checkpoints and other cell cycle controls that operate in eukaryotic cells. This is followed by a discussion of how the cell cycle provides not only a...