Kinetochore Spindle Interaction in Fission Yeast

裂殖酵母中动粒纺锤体的相互作用

• 批准号: 6673793
• 负责人: XIANGWEI HE
• 金额: $ 25.28万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6673793
• 关键词: Schizosaccharomyces pombe; cell cycle; centromere; cytogenetics; functional /structural genomics; fungal genetics; gene targeting; genetic library; genetic screening; green fluorescent proteins; immunoprecipitation; microtubules; mitotic spindle apparatus; protein purification; protein structure function; spindle pole body; temperature sensitive mutant

DESCRIPTION (provided by applicant): Equal chromosome segregation in mitosis requires proper interaction between the chromosomes and the mitotic spindle. Kinetochores are the specialized structures that are assembled on centromeric DNAs and mediate the attachment between the chromosomes and the spindle microtubules. Kinetochores of various organisms differ remarkably in their architectures and yet perform fundamentally similar functions. Much has been learnt of the kinetochores in S. cerevisiae. However, it is unclear to what extent can we apply the knowledge of this simple point kinetochore onto complex regional kinetochores such as those of humans. The long-term goal of this proposal is to dissect the kinetochore structure in S. pombe as a model of the regional kinetochores and to understand how kinetochores co-ordinate with the spindle to ensure the high fidelity of chromosome segregation in this model organism. By comparing and contrasting the kinetochores of S. pombe, S. cerevisiae and those of other organisms, we wish to delineate the general biological principles of the kinetochore functions. This knowledge will facilitate the identification of the molecular lesions in tumor cells which lead to high rate of aneuploidy - erroneous chromosome numbers that are detected in virtually all types of tumor. Three specific aims are proposed here to analyze the kinetochore/spindle interaction in fission yeast: 1. To identify novel kinetochore and spindle components in fission yeast that are required for their proper attachment. 2. To characterize the architectural and functional roles of novel kinetochore proteins. 3. To explore the mechanism of how kinetochores switch from a static affinity to spindle pole to a dynamic affinity to spindle MTs at the entry of mitosis.

描述（由申请方提供）：有丝分裂中的染色体均等分离需要染色体与有丝分裂纺锤体之间的适当相互作用。着丝粒是着丝粒DNA上的特化结构，介导染色体与纺锤体微管的连接。不同生物体的动粒在结构上有显著的差异，但功能基本相似。关于S.酿酒的。然而，目前还不清楚我们能在多大程度上将这种简单的点动粒的知识应用于复杂的区域动粒，如人类的动粒。这项计划的长期目标是解剖S.粟酒裂殖酵母作为一个模型的区域动粒，并了解如何动粒协调与纺锤体，以确保高保真的染色体分离，在这个模式生物。通过对S. pombe，S.酿酒酵母和其他生物的，我们希望描绘动粒功能的一般生物学原理。这一知识将有助于识别肿瘤细胞中的分子病变，这些病变导致高比率的非整倍体-在几乎所有类型的肿瘤中检测到的错误染色体数目。这里提出了三个具体的目标来分析分裂酵母中的动粒/纺锤体相互作用： 1.确定新的着丝粒和纺锤体组件在分裂酵母，需要他们正确的连接。 2.描述新型动粒蛋白的结构和功能。 3.探讨在有丝分裂开始时，着丝粒由对纺锤体极的静态亲和转变为对纺锤体MT的动态亲和的机制。