Regulation of Kinetochore Assembly

着丝粒组装的调控

• 批准号: 6487120
• 负责人: ANDREA R CASTILLO
• 金额: $ 3.83万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-16 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6487120
• 关键词: Saccharomyces cerevisiae; cell component structure /function; cell cycle; centromere; fungal genetics; fungal proteins; genetic regulation; immunoprecipitation; intermolecular interaction; microtubules; mitotic spindle apparatus; molecular assembly /self assembly; nucleoproteins; postdoctoral investigator; protein structure function

DESCRIPTION (provided by applicant) Accurate segregation of replicated chromosomes is critical for cells to maintain genomic stability. Chromosome missegregation has been associated with the majority of human cancers. Segregation is facilitated in part by the kinetochore, a protein complex that connects the centromere of chromosomes to the microtubules of the mitotic spindle. The work described in this proposal uses Saccharomyces cerevisiae to address regulatory and assembly requirements for kinetochores on endogenous and "new" centromeres. Cell cycle requirements for kinetochore assembly will be determined by asking if kinetochore proteins can incorporate into kinetochores while the cells are held in G1, S, or M of the cell cycle. Conditional centromeres, not available in multicellular eukaryotes, will also be used here to identify epigenetic factors that may distinguish endogenous from "new" kinetochores. Finally, an epistasis analysis among kinetochore proteins will establish a dependence for assembly relationship between among the kinetochore proteins. Since many of the kinetochore proteins are conserved between S. cerevisiae and other eukaryotes, these studies can be extended to other organisms.

描述（由申请人提供） 复制染色体的精确分离对于细胞 保持基因组的稳定性。染色体错误分离与 大多数人类癌症。隔离部分是由 着丝粒，一种蛋白质复合物，连接染色体的着丝粒， 有丝分裂纺锤体的微管本提案中所述的工作 使用酿酒酵母来满足监管和组装要求 内源性和“新的”着丝粒上的着丝粒。细胞周期要求 将通过询问动粒蛋白质是否 当细胞处于G1、S或M期时， 细胞周期条件着丝粒，在多细胞中不可用 真核生物，也将在这里使用，以确定表观遗传因素， 区分内源性和“新的”动粒。最后，上位性分析 在动粒蛋白质之间将建立一种依赖性， 动粒蛋白之间的关系。由于许多 动粒蛋白在S.酿酒酵母和其它真核生物， 这些研究可以扩展到其他生物。