ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT

染色体运动的分析和控制

基本信息

  • 批准号:
    6829090
  • 负责人:
  • 金额:
    $ 23.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1976
  • 资助国家:
    美国
  • 起止时间:
    1976-01-01 至 2006-11-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (Verbatim from the applicant's abstract): 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. The movement is powered by motile kinetochores (the structures that attach the chromosome to spindle microtubules). Kinetochores switch between pulling and an inactive, 'neutral' state. The switch may be regulated by tension, which will be tested directly by pushing on chromosomes with a micromanipulation needle to relax the tension and allow switching to occur. The motors dynein and CENP-E are present at kinetochores when chromosomes begin to move but are later lost from the chromosomes. The possible uses for such transitory kinetochore motors will be tested. 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 possibility that the poles are the sensitive site will be tested by micromanipulation. Errors of the second sort are avoided by a checkpoint that detects errors and delays the completion of mitosis. Tension-sensitive kinetochore protein phosphorylation may be the signal to the checkpoint. Tension certainly causes kinetochore dephosphorylation, but the effect may be direct (deformation of some component) or indirect (tension increases the number of microtubules, which may lead to dephosphorylation). This ambiguity will be resolved by creating a situation in which tension can be manipulated yet does not increase the number of microtubules. The effect of tension on the structure of the kinetochore and its components will be explored by combining micromanipulation to vary the tension force with electron microscopy to view the consequences. Kinetochores will be reconstructed by threedimensional tomography. The ultimate goal is to understand how tension, by altering structure, can lead to chemical changes such as dephosphorylation.
描述(申请人摘要的逐字记录):目标是理解 精确的染色体运动和染色体的精确分配 子细胞进行有丝分裂和减数分裂。分配错误可能会导致 癌症以及唐氏综合症和其他人类染色体疾病。细胞如何 避免错误是这个项目的主题。有丝分裂产生的机械张力 力量是关键。在有丝分裂早期,染色体移动到一个相当位置 正好位于主轴两极之间的中间。运动由动力驱动 着丝粒(将染色体附着在纺锤体上的结构) 微管)。着丝粒在拉动和不活跃的“中性”之间切换 状态。开关可采用拉力调节,可直接测试 用显微操作针推动染色体以放松张力 允许发生切换。电机动力蛋白和 CENP-E 存在于 当染色体开始移动但后来从染色体中丢失时,称为着丝粒 染色体。这种瞬态着丝粒马达的可能用途是 已测试。染色体分布中常见的错误有两类: 避免这两者都涉及紧张。避免第一类错误 取决于染色体对纺锤体的锚定,该锚定对 紧张。将测试两极为敏感点的可能性 通过显微操作。检查点可以避免第二类错误 检测错误并延迟有丝分裂的完成。张力敏感 动粒蛋白磷酸化可能是检查点的信号。 紧张肯定会导致动粒去磷酸化,但其影响可能是 直接(某些部件的变形)或间接(张力增加 微管的数量,这可能导致去磷酸化)。这种暧昧 将通过创造一种可以操纵紧张局势的情况来解决 但不会增加微管的数量。张力对的影响 着丝粒的结构及其组成部分将通过结合来探索 显微操作改变张力,用电子显微镜观察 后果。着丝粒将通过三维重建 断层扫描。最终目标是了解张力如何通过改变 结构,可导致化学变化,例如去磷酸化。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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R. BRUCE NICKLAS其他文献

R. BRUCE NICKLAS的其他文献

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{{ truncateString('R. BRUCE NICKLAS', 18)}}的其他基金

ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    2415063
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    6624978
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    2910014
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    3268547
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    3268544
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    2168737
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    3268551
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    3268543
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    3268542
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:
ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT
染色体运动的分析和控制
  • 批准号:
    6285802
  • 财政年份:
    1976
  • 资助金额:
    $ 23.1万
  • 项目类别:

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