MAMMALIAN CELL CYCLE CHECKPOINT GENES

描述：细胞周期检查点将细胞分裂周期停止在 特定的阶段，因此DNA修复途径可以恢复 基因组。检查点通路中的缺陷可导致基因组不稳定和 会导致癌症。一种名为hsrad17的人类cdna已被克隆为人类 裂解酵母rad17的同源物，它是酵母S. Pombe DNA损伤/复制阻断检查点通路。的目标是 这项建议是根据hsrad17的检查点功能来描述其特征 在哺乳动物细胞中，以及它作为肿瘤抑制因子的可能作用。 反义技术和抗体的引入将被用于 耗尽hsrad17蛋白，它在检查点控制中的作用将得到测试。 Hsrad17基因座将被映射到人类染色体上。Loh和Posable 将对癌症中的hsrad17突变进行调查。基因筛查将是 用于分离与hsrad17基因产物相互作用的蛋白质以 确定它的功能和它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.