ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT

我们的目标是了解精确的染色体运动和准确的 有丝分裂和减数分裂中染色体对子细胞的分布。 分布错误可能会导致癌症、唐氏综合症等 人类的染色体紊乱。单元格如何避免错误是 这个项目。有丝分裂力量产生的机械张力是关键。 在有丝分裂的早期，染色体移动到非常精确的中途位置。 在主轴两极之间。张力调节的推拉电机 可能对这场运动负有责任。马达和他们的规则将会 在材料上的特点应该揭示他们的行动 很明显。张力的作用将通过拉紧来直接测试 用微操作针增加或减少染色体 紧张。产生染色体运动的力量将在 绝对单位。活细胞的这些特性将与 对当前受欢迎的精确染色体模型的期望 有动静。 染色体分布中常见的错误有两种，一种是张力 参与了避免这两种情况的发生。避免第一类错误 取决于染色体对纺锤体的锚定，该纺锤体对 紧张。将寻找锚地的来源，并将其敏感性 张力将通过微操作进行测试。第二类错误是 通过检测何时没有紧张局势的检查站来避免。紧张-- 敏感蛋白的磷酸化可能是通向检查点的信号。这个 将寻求对紧张敏感的生化活动。一个 首先将测试染色体激酶的活性，看看它是否 在实验中改变张力时会受到影响。一种智能网的开发 可以进行机械和生化操作的体外系统 联合提出，目的是将有丝分裂力量与 检查站的生物化学。

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.