Chromosome Movement in Meiosis and Mitosis

减数分裂和有丝分裂中的染色体运动

• 批准号: 7193383
• 负责人: Sharyn A. Endow
• 金额: $ 27.45万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7193383
• 关键词: Chromosome; Movement; Meiosis; Mitosis

DESCRIPTION (provided by applicant): The long-term objectives of this project are to identify and characterize the forces that underlie chromosome movement in meiosis and mitosis, including interactions of the chromosomes with the spindle and microtubule dynamics involved in spindle assembly and function. A major goal is to understand the role of microtubule motor proteins in spindle and chromosome dynamics during cell division, including the molecular basis of motor directionality and force generation, and the importance of these motor properties in division. The proposed studies focus on Ncd, a minus-end kinesin microtubule motor protein of Drosophila. The Ncd motor plays an essential role in spindle assembly and function in meiosis and mitosis. The studies proposed here are to examine basic motor properties with the objective of understanding how motors work in the cell. The specific aims of the proposed studies are to 1. Determine the structural basis of motor directionality. The region of the Ncd motor that undergoes a conformational or angle change required for motor directionality will be determined. 2. Identify structural changes of the motor essential for function. Mutants that decouple motor functions or alter the nucleotide hydrolysis cycle will be analyzed to obtain crystal structures of new motor conformations and provide information about the motor mechanism. 3. Define factors essential for motor function in live cells. A mutant that converts the motor into a bidirectional motor in vitro will be analyzed in live cells to examine the hypothesis that motor directionality is essential to Ncd function in the spindle. These studies address the molecular basis of force generation in the spindle and the role of microtubule motors in chromosome movement during cell division. Defective chromosome distribution causes aneuploidy and other genetic abnormalities, and is associated with oncogenesis in humans.

描述（由申请人提供）：该项目的长期目标是识别和表征减数分裂和有丝分裂中染色体运动的力，包括染色体与纺锤体组装和功能所涉及的纺锤体和微管动态的相互作用。一个主要目标是了解细胞分裂过程中微管运动蛋白在纺锤体和染色体动力学中的作用，包括运动方向性和力产生的分子基础，以及这些运动性能在分裂中的重要性。拟议的研究集中于NCD，NCD是果蝇的负端微管运动蛋白。 NCD电动机在减数分裂和有丝分裂中的主轴组件和功能中起着至关重要的作用。此处提出的研究是检查基本运动性能，目的是了解电动机在细胞中的工作方式。 拟议研究的具体目的是 1。确定运动方向性的结构基础。将确定经历运动方向性所需的构象或角度变化的NCD电动机区域。 2。确定电动机的结构变化。将分析将运动功能或更改核苷酸水解周期的突变体进行分析，以获得新的运动构象的晶体结构并提供有关运动机制的信息。 3。定义活细胞中运动功能必不可少的因素。将在活细胞中分析将电动机转换为双向电动机的突变体，以检查运动方向性对于纺锤体中的NCD功能至关重要的假设。 这些研究介绍了力在纺锤体中产生力的分子基础以及微管电动机在细胞分裂过程中染色体运动中的作用。有缺陷的染色体分布会导致非整倍性和其他遗传异常，并且与人类的肿瘤发生有关。