MAMMALIAN CELL CYCLE CHECKPOINT GENES

描述：细胞周期检查点阻止细胞分裂周期， 因此DNA修复途径可以恢复细胞的完整性。 基因组 检查点途径中的缺陷可导致基因组不稳定性， 导致癌症。 一个名为hsrad 17的人类cDNA已被克隆为人类 裂殖酵母rad 17的同源物，是酵母S. 粟酒裂殖酵母DNA损伤/复制阻断检查点途径。 的目标 该建议是根据其检查点功能来表征HSRAD 17 在哺乳动物细胞中，以及其作为肿瘤抑制剂的可能作用。 反义技术和抗体的引入将用于 耗尽hsrad 17蛋白，并测试其在检查点控制中的作用。 hsrad 17基因座将被定位到人类染色体上。 洛缺失和可能 将研究癌症中的hSRAD 17突变。 基因筛查将是 用于分离与hsrad 17基因产物相互作用的蛋白质， 决定其功能和参与的细胞周期途径。

DESCRIPTION: Cell cycle checkpoints arrest the cell division cycle at specific stages so DNA repair pathways can restore the integrity of the genome. Defects in checkpoint pathways can cause genomic instability and lead to cancer. A human cDNA, called hsrad17, has been cloned as the human homologue of fission yeast rad17, an essential component of the yeast S. pombe DNA damage/replication block checkpoint pathway. The objective of this proposal is to characterize hsrad17 in terms of its checkpoint function in mammalian cells, as well as its possible role as a tumor suppressor. Antisense technology and the introduction of antibodies will be used to deplete hsrad17 protein, and its role in checkpoint control will be tested. The hsrad17 locus will be mapped to a human chromosome. LOH and possible hsrad17 mutations in cancer will be investigated. Genetic screens will be used to isolate proteins that interact with the hsrad17 gene product to determine its function and the cell cycle pathways in which it is involved.