ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT

染色体运动的分析和控制

• 批准号: 2415063
• 负责人: R. BRUCE NICKLAS
• 金额: $ 17.98万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-01-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2415063
• 关键词: Orthoptera; biomechanics; birefringences; cell cycle; cell type; centromere; chromosome movement; cinemicrography; computer simulation; electron microscopy; fluorescence microscopy; image enhancement; kinetosome; mechanical stress; meiosis; micromanipulator; microtubules; mitotic spindle apparatus; nuclear membrane; phase contrast microscopy; phosphorylation; tissue /cell culture

The goal is to understand precise chromosome movement and the accurate distribution of chromosomes to the daughter cells in mitosis and meiosis. Errors in distribution can lead to cancer and to Down syndrome and other chromosome disorders in humans. How cells avoid errors is the subject of this project. Mechanical tension from mitotic forces is the key. Early in mitosis, chromosomes move to a position quite precisely midway between the spindle poles. Pushing and pulling motors regulated by tension may be responsible for this movement. The motors and their regulation will be characterized in materials that should reveal their action very clearly. The role of tension will be tested directly by pulling on chromosomes with a micromanipulation needle to increase or decrease the tension. The forces that produce chromosome movement will be measured in absolute units. These properties of living cells will be compared with expectations from the currently favored model for precise chromosome movement. The common errors in chromosome distribution are of two sorts, and tension is involved in avoiding both of them. Avoiding errors of the first sort depends on an anchorage of chromosomes to the spindle that is sensitive to tension. The source of the anchorage will be sought and its sensitivity to tension will be tested by micromanipulation. Errors of the second sort are avoided by a checkpoint that detects when tension is absent. Tension- sensitive protein phosphorylation may be the signal to the checkpoint. The biochemical activity that is sensitive to tension will be sought. A chromosomal kinase activity will be tested first, by seeing if it is affected when tension is altered experimentally. Development of an in vitro system in which mechanical and biochemical manipulations can be combined is proposed, with the aim of connecting mitotic forces with the biochemistry of the checkpoint.

其目标是了解精确的染色体运动和准确的 在有丝分裂和减数分裂中染色体向子细胞的分配。 分布上的错误会导致癌症、唐氏综合症和其他疾病。 人类的染色体疾病细胞如何避免错误是 这个项目有丝分裂力产生的机械张力是关键。 在有丝分裂的早期，染色体精确地移动到 在主轴杆之间。张力调节的推拉电机 可能是造成这种运动的原因电动机及其调节将 以材料为特征，这些材料应该非常清楚地揭示它们的作用， 清楚拉力的作用将直接通过拉上 染色体与显微操作针，以增加或减少 张力产生染色体运动的力将在 绝对单位活细胞的这些特性将与 从目前流行的精确染色体模型的期望 运动 染色体分布中常见的错误有两种， 都是为了避免这两种情况避免第一类错误 依赖于染色体对纺锤体的锚定， 张力将寻找锚点的来源， 将通过显微操作测试张力。第二类错误是 通过检查点检测何时不存在张力来避免。紧张- 敏感蛋白磷酸化可能是检查点的信号。的 将寻找对张力敏感的生化活性。一 首先将测试染色体激酶活性，看看它是否 当张力被实验性地改变时会受到影响。开发一种 体外系统，其中机械和生物化学操作可以 结合提出，目的是连接有丝分裂部队与 检查点的生物化学。