Chromosome Movement in Meiosis and Mitosis

描述（由申请人提供）：该项目的长期目标是确定和描述减数分裂和有丝分裂中染色体运动的基础力量，包括染色体与纺锤体的相互作用以及纺锤体组装和功能中涉及的微管动力学。一个主要的目标是了解微管运动蛋白在细胞分裂过程中的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。拟开展的研究主要集中在果蝇的负端运动蛋白Ncd上。Ncd马达在纺锤体组装和减数分裂和有丝分裂中起重要作用。这里提出的研究是为了检查基本的运动特性，目的是了解运动是如何在细胞中工作的。

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.