Kinetochore Spindle Interaction in Fission Yeast

裂殖酵母中动粒纺锤体的相互作用

• 批准号: 6931574
• 负责人: XIANGWEI HE
• 金额: $ 26.34万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 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 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6931574
• 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（由申请人提供）：有丝分裂中的同等染色体分离需要染色体和有丝分裂纺锤体之间的适当相互作用。动粒是在着丝粒 DNA 上组装的特殊结构，介导染色体和纺锤体微管之间的附着。各种生物体的着丝粒在结构上显着不同，但执行的功能基本相似。人们对酿酒酵母的着丝粒了解很多。然而，目前尚不清楚我们可以在多大程度上将这种简单点动粒的知识应用到复杂的区域动粒（例如人类的动粒）上。该提案的长期目标是剖析粟酒裂殖酵母的着丝粒结构作为区域着丝粒的模型，并了解着丝粒如何与纺锤体协调以确保该模型生物中染色体分离的高保真度。通过比较和对比粟酒裂殖酵母、酿酒酵母和其他生物体的动粒，我们希望描述动粒功能的一般生物学原理。这些知识将有助于识别肿瘤细胞中的分子损伤，这些损伤会导致高比例的非整倍性——几乎在所有类型的肿瘤中都能检测到错误的染色体数目。这里提出了三个具体目标来分析裂殖酵母中着丝粒/纺锤体的相互作用： 1. 鉴定裂殖酵母中正确附着所需的新型动粒和纺锤体成分。 2. 表征新型动粒蛋白的结构和功能作用。 3. 探讨有丝分裂入口处动粒如何从与纺锤体极的静态亲和力转变为与纺锤体微管的动态亲和力的机制。