Abstract

Cell division is the most complex process undertaken by a single cell and must be stringently regulated to maintain fidelity of reproduction. Proliferative cells are in a continuous loop or cycle composed of four stages: S, during which DNA synthesis occurs, M (mitosis), G1 and G2. The gap phases G1 and G2 are growth and regulatory periods which are required to assure fidelity of the synthetic and division processes, as illustrated in Figure 5.1 (1). Gi is required for most cell types to complete cell growth. A critical checkpoint in G1, called START in yeast or the restriction point in mammalian cell, is the point in the cycle at which the cell commits to DNA replication (2). Both positive and negative signals operate at this point to determine whether the cell continues through the cycle (3). G2 is necessary to assure that DNA synthesis is complete to initiate mitosis and can be extended if DNA replication is incomplete or DNA has been damaged. In the rapidly dividing cells of early embryogenesis following fertilization, the cell cycle and G1 are short because no cell growth is required (4). Much of the research on the cell cycle has been done in unicellular eukaryotic organisms, particularly yeast. Control of the cell cycle in the unicellular organism is relatively simple because their cellular requirements are simple. They respond primarily to cues concerning nutrition and proliferation. In contrast, cells of multicellular organisms must be regulated by the overall needs of the organism. Thus, many cell types are required to be in a quiescent state (Go) most of their life. Other cell types are transiently proliferative and undergo cycles of cell growth and cell death according to the needs of the organism. Multicellular organisms have therefore evolved a highly complex set of mechanisms for regulating the cell cycle, which must then be integrated with all of the processes involved in cell growth and division.

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