MAMMALIAN CELL CYCLE CHECKPOINT GENES

哺乳动物细胞周期检查点基因

• 批准号: 2448374
• 负责人: LEI LI
• 金额: $ 9.38万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-15 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2448374
• 关键词: DNA damage; DNA repair; DNA replication; Saccharomyces cerevisiae; Schizosaccharomyces pombe; animal genetic material tag; antibody formation; antisense nucleic acid; cell cycle; cell line; electroporation; fluorescent in situ hybridization; gene targeting; genetic mapping; human genetic material tag; laboratory mouse; molecular cloning; neoplasm /cancer genetics; tumor suppressor genes; yeast two hybrid system

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.

描述：细胞周期检查点阻止在 特定阶段，因此DNA修复途径可以恢复 基因组。 检查点途径中的缺陷会导致基因组不稳定性，并且 导致癌症。 一个称为HSRAD17的人cDNA被克隆为人类 裂变酵母Rad17的同源物，这是酵母菌的重要组成部分 POMBE DNA损坏/复制块检查点途径。 目的 该建议是根据其检查点功能来表征HSRAD17 在哺乳动物细胞中，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 将测试HSRAD17蛋白质及其在检查点控制中的作用。 HSRAD17基因座将映射到人类染色体。 loh和可能 将研究HSRAD17癌症中的突变。 遗传屏幕将是 用于分离与HSRAD17基因产物相互作用的蛋白质 确定其功能和所涉及的细胞周期途径。