Molecular Analysis of the Spindle Pole Body

主轴极体的分子分析

基本信息

批准号：
7498247
负责人：
Trisha N. Davis
金额：
$ 4.56万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 2011-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7498247
关键词：
Affect Animal Model Architecture Behavior Cell Cycle Cell Death Cell division Cells Chromosome Segregation Chromosomes Class Collaborations Complex Computer software Condition Congenital Abnormality Core Protein Eukaryotic Cell Fluorescence Resonance Energy Transfer Funding Genes Genetic Materials Genetic Screening Grant Human In Vitro Insecta Kinetochores Life Measures Microtubule-Organizing Center Microtubules Modeling Molecular Analysis Motor Mutagenesis Mutation Nuclear Pore Organism Period Analysis Phenylalanine Phosphorylation Site Phosphotransferases Plus End of the Microtubule Point Mutation Process Protein Dynamics Proteins Regulation Research Personnel Resolution Role Saccharomyces cerevisiae Serine Structure Testing Time Tubulin Work Yeasts aurora B kinase design human TYRP1 protein in vivo insight interest mathematical model mutant novel particle physical property programs protein purification reconstruction research study spindle pole body tomography tool tumorigenesis yeast protein yeast two hybrid system

项目摘要

Accurate chromosome segregation is required for propagation of all cells. Errors in this process are implicated in oncogenesis, birth defects and cell death. Crucial to proper partitioning of the chromosomes during cell division is the establishment, arrangement and then breakdown of a bipolar spindle. The aim of this grant is to further understand the structure, assembly and dynamics of the proteins that create and control the organization of the spindle in the model organism Saccharomyces cerevisiae. The microtubule organizing center in yeast is the spindle pole body (SPB). The SPB is a dynamic structure that undergoes remodeling in a cell-cycle specific manner. We have identified proteins involved in the remodeling process and will characterize them. We have provided a detailed architectural description of the SPB and will continue our structural analysis. The SPB nucleates and organizes microtubules. We will perform a set of experiments designed to distinguish between two current models for nucleation. Finally, we have found that kinetochores can biorient without being attached to the plus-end of microtubules. New insights into biorientation will be obtained from determining the role of kinetochores, motors and other spindle proteins in the formation of the bipolar spindle when plus-end attachment is not involved. Because many proteins and spindle features are conserved from yeast to human, our studies will inform models of how eukaryotic cells correctly distribute their genetic material.

所有细胞的繁殖都需要准确的染色体分离。这个过程中的错误有与肿瘤发生、出生缺陷和细胞死亡有关。对于染色体的正确分配至关重要细胞分裂期间是双极纺锤体的建立、排列和分解。的目的这笔资助是为了进一步了解蛋白质的结构、组装和动力学，这些蛋白质创造和控制模型生物酿酒酵母中纺锤体的组织。微管酵母的组织中心是纺锤体极体（SPB）。 SPB 是一个动态结构，以细胞周期特定方式进行重塑。我们已经鉴定出参与重塑过程的蛋白质并将描述它们的特征。我们提供了 SPB 的详细架构描述，并将继续我们的结构分析。 SPB 使微管成核并组织。我们将执行一组旨在区分两种当前成核模型的实验。最后，我们发现着丝粒可以生物定向而不附着在微管的正端。新见解通过确定动粒、马达和其他纺锤体蛋白的作用，可以获得生物定向。当不涉及正端附件时双极纺锤体的形成。因为许多蛋白质和纺锤体特征从酵母到人类都是保守的，我们的研究将为模型提供真核细胞如何正确分配他们的遗传物质。