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: 7027078
• 负责人: Sharyn A. Endow
• 金额: $ 28.27万
• 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 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7027078
• 关键词: Drosophilidae; X ray crystallography; adenosinetriphosphatase; cell cycle; chromosome movement; conformation; cryoelectron microscopy; growth /development; intermolecular interaction; kinesin; meiosis; microtubule associated protein; microtubules; mitotic spindle apparatus; protein structure function; tissue /cell culture; tubulin; video microscopy; western blottings

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作用力，包括染色体与纺锤体的相互作用以及参与纺锤体组装和功能的微管动力学。一个主要目标是了解微管运动蛋白在细胞分裂过程中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，以及这些运动特性在分裂中的重要性。拟议的研究重点是 Ncd，果蝇的负端驱动蛋白微管运动蛋白。 Ncd 马达在纺锤体组装以及减数分裂和有丝分裂的功能中发挥着重要作用。这里提出的研究是检查基本的运动特性，目的是了解运动在细胞中的工作原理。 拟议研究的具体目标是 1.确定运动方向性的结构基础。将确定 Ncd 电机中经历电机方向性所需的构象或角度变化的区域。 2. 识别电机功能所必需的结构变化。将分析解耦运动功能或改变核苷酸水解循环的突变体，以获得新运动构象的晶体结构并提供有关运动机制的信息。 3. 定义活细胞运动功能所必需的因素。将在活细胞中分析在体外将电机转化为双向电机的突变体，以检验运动方向性对于纺锤体 Ncd 功能至关重要的假设。 这些研究探讨了纺锤体中力产生的分子基础以及微管马达在细胞分裂过程中染色体运动中的作用。染色体分布缺陷会导致非整倍体和其他遗传异常，并与人类肿瘤发生有关。