G2 phase cdk2/cyclin A co-ordinates multiple pathways in G2/M progression

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Cell growth is a tightly regulated process that ensures the exact duplication of the entire genomic DNA followed by division of the cell into two identical daughter cells. If this strict ordering of events is in any way disrupted, the resultant daughter cells would have a different complement of DNA from their parent cell, essentially mutant cells. The cell has established a mechanism to ensure the correct ordering of these crucial events, known as the cell cycle, and mechanisms that can respond to disruptions in this ordering and halt the normal cell cycle mechanism until the fault is rectified. These are the checkpoint controls. Checkpoint controls also respond to environmental stresses such as toxins that can damage the DNA to produce mutations. In diseases such as cancer, these checkpoint mechanisms are often faulty, allowing the cells to accumulate DNA mutations which can ultimately result in the cells becoming the aggresive, malignant tumours associated with the worst forms of this disease. Thus a detailed understanding of the cellular mechanisms involved in normal cell cycle and checkpoint control is important in not only defining the causes of these diseases at a molecular level, but may ultimately provide molecular targets for drugs that specifically destroy cancer cells by targeting the faulty checkpoint control. This proposal will investigate one component of the cell cycle mechanism, cdk2-cyclin A, which also has a major role in checkpoint control, to determine its exact role in both these important cellular growth controls.