MITOSIS COUPLING TO COMPLETION OF DNA REPLICATION

在体细胞中，有丝分裂在DNA合成之前不会发生。 完成. 然而，这种依赖性可以被突变或 化学处理表明其通过对照正常维持 机制等 这些类型的控制机制被称为 "检查站"。 （一）.连接有丝分裂和DNA完成的检查点 复制确保细胞能够在S期停滞期存活 由于暴露于DNA合成抑制剂或DNA损伤。 由于此类抑制剂经常用于化疗，因此重要的是 来了解这种控制是如何工作的。 的具体目标 这里提出的实验是使用 裂殖酵母，粟酒裂殖酵母，作为模型系统。 为 控制细胞周期的基本机制是高度保守的 在演变过程中，所获得的结果可能适用于所有 真核细胞 有丝分裂与DNA复制的结合需要一个 细胞内传感通路：控制有丝分裂的蛋白质必须 "接收"有关染色体的信息。 以前的工作已经建立了 高度保守的有丝分裂调节因子cdc2在 这个过程 已知调节cdc2活化的其它蛋白质是 也参与其中。 最近，编码蛋白质的新基因（hus和rad基因） 在途径的早期起作用。 这些蛋白质 可能参与"信号" cdc2，复制是 不完整 建议使用可用的突变体来确定 这些"信号"是什么以及它们如何被cdc2使用 结合分子、遗传和生物化学技术。 在 此外，还提出了确定新的基因功能，连接这些 两个过程。

In somatic cells, mitosis does not occur before DNA synthesis is complete. However, this dependence can be disrupted by mutations or chemical treatments indicating that it is maintained normally by control mechanisms. These types of control mechanisms have been termed "checkpoints". (1). The checkpoint coupling mitosis to completion of DNA replication ensures that cells can survive periods of S-phase arrest resulting from exposure to inhibitors of DNA synthesis or DNA damage. As such inhibitors are frequently used in chemotherapy, it is important to understand how this control works. The specific aim of the experiments proposed here is to investigate this checkpoint using the fission yeast, Schizosaccharomyces pombe, as a model system. As the basic mechanisms controlling the cell cycle have been highly conserved during evolution, results obtained are likely to be applicable to all eukaryotic cells. Coupling of mitosis to completion of DNA replication requires an intracellular sensing pathway: proteins that control mitosis must "receive" information about chromosomes. Previous work has established that the highly conserved mitotic regulator cdc2 plays a central role in this process. Other proteins known to regulate activation of cdc2 are also involved. Recently, new genes (hus and rad genes) encoding proteins acting early in the pathway have been identified. these proteins are likely to be involved in "signalling" cdc2 that replication is incomplete. It is proposed to use the available mutants to determine what these "signals" are and how they are "detected" by cdc2 using a combination of molecular, genetic and biochemical techniques. In addition, it is proposed to identify novel gene functions that link these two processes.