The Oncologist Fundamentals of Cancer MedicineThe cell cycle is a highly ordered process that results in the duplication and transmission of genetic information from one cell generation to the next. During the process DNA must be accurately replicated and identical chromosomal copies distributed to two daughter cells. The cell cycle is divided into discrete phases: G 1 (gap 1) is the interval or gap between mitosis (M phase) and DNA synthesis (S phase). During G 1 the cell is subject to stimulation by extracellular mitogens and growth factors; in response to these stimuli, the cell passes through G 1 and proceeds with DNA synthesis in S phase; G 2 (gap 2) is the interval between the completion of DNA synthesis (S) and mitosis; M phase is marked by the generation of bipolar mitotic spindles, segregation of sister chromatids and cell division. The regulation of the cell cycle must ensure that the events in each phase are complete before moving to the next. Thus checkpoints for monitoring the integrity of DNA are strategically placed in late G 1 and at the G 2 /M interface to prevent progression and propagation of mutated or damaged cells. G 0 refers to cells that are quiescent (temporarily or permanently out of cycle). The normal cell is dependent on external stimuli (mitogens or growth factors) to move it out of G 0 and through the early part of G 1 . The cell responds to these external stimuli, communicated through a cascade of intracellular phosphorylations, by upregulating expression of the cyclins which associate with the cyclin-dependent kinases (CDKs). The time periods shown in Figure 1 are generic and only indicate the relative duration of each phase.The cell cycle is propelled by a series of protein kinases; these CDKs complex with their respective cyclin and, subsequently, are phosphorylated by an activating kinase. Cyclin is the regulatory unit and CDK is its catalytic partner.Cyclins, with their bound and activated CDKs, function during distinct stages of the cell cycle. As the name suggests, the level of each cyclin independently increases or decreases within the phases of the cycle. Cyclin/CDK complexes phosphorylate specific protein substrates to move the cell through the cycle with activation of DNA synthesis (in late G 1 and S), and formation of the structural components associated with mitosis (in late G 2 and M). The periodicity of the cyclins, mediated by their synthesis and subsequent proteolytic degradation, ensure the well-delineated transitions between cell cycle stages. Because errors encoded in the genome may result in defective clones, close monitoring of the cell cycle for abnormal Figure 1. The Cell Cycle-Times are relative.