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

细胞生长是一个严格控制的过程，确保整个基因组DNA的准确复制，然后将细胞分裂成两个相同的子细胞。如果这种严格的事件顺序以任何方式被打乱，由此产生的子细胞将拥有与其母细胞不同的DNA补充，本质上是突变细胞。细胞已经建立了一种机制来确保这些关键事件的正确排序，即细胞周期，以及可以对这种顺序的中断做出反应的机制，并停止正常的细胞周期机制，直到故障得到纠正。这些是检查站控制。检查站控制也会对环境压力做出反应，例如可以破坏DNA产生突变的毒素。在癌症等疾病中，这些检查点机制通常是有缺陷的，允许细胞积累DNA突变，最终可能导致细胞成为与这种疾病最严重形式有关的侵袭性恶性肿瘤。因此，对正常细胞周期和检查点控制所涉及的细胞机制的详细了解不仅对于在分子水平上确定这些疾病的原因很重要，而且最终可能为通过靶向错误的检查点控制而特异性地摧毁癌细胞的药物提供分子靶点。这项建议将研究细胞周期机制的一个组成部分，CDK2-细胞周期蛋白A，它也在检查点控制中发挥重要作用，以确定其在这两个重要的细胞生长控制中的确切作用。

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.