STUDIES ON CENTROMERE STRUCTURE AND FUNCTION

着丝粒结构与功能的研究

• 批准号: 3163426
• 负责人: John A Carbon
• 金额: $ 26.62万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3163426
• 关键词: Aspergillus; DNA; RNA; Saccharomyces; binding proteins; centromere; clone cells; electron microscopy; fungal genetics; gel filtration chromatography; gene expression; genetic manipulation; genetic mapping; genetic operator element; genetic promoter element; genetic transcription; laboratory rabbit; meiosis; microtubules; molecular cloning; nucleic acid hybridization; nucleic acid sequence; protein structure; radiotracer; regulatory gene; ribosomal RNA; structural genes; transfer RNA; tritium; tubulin; ultracentrifugation

The objectives are to define the structural organization of the centromere regions of eukaryotic chromosomes, and to understand the molecular mechanisms involved in chromosome segregation during mitotic and meiotic cell divisions. The centromere studies supported by this grant are carried out using as experimental systems the budding yeast, Saccharomyces cerevisiae, and the filamentous fungus, Aspergillus nidulans. Synthetic minichromosomes, containing a functional centromere (CEN), a DNA replicator function, and telomeric DNA (if linear), constitute invaluable probes for the study of chromosome structure and function. Specific aims include: (1) the construction of structurally altered centromere DNAs with altered function, using in vitro mutagenesis techniques; (2) the identification of genes specifying kinetochore structural proteins or gene products necessary for formation of the yeast kinetochore; (3) the isolation and characterization of kinetochore proteins (centromere binding proteins); (4) investigation of the mechanism of kinetochore-microtubule associations; (5) investigation of specialized DNA structures in the centromere region, including replicative intermediates, kinked DNA, and methylated DNA; (6) isolation and structural characterization of centromere DNAs from Aspergillus nidulans, as a step toward an understanding of centromere structure-function in more complex organisms. Studies on the molecular mechanisms involved in cell division and chromosome segregation in the experimentally tractable lower eukaryotes offer an approach to an understanding of analogous mechanisms as they function normally and abnormally in higher organisms.

目标是定义着丝粒的结构组织 真核染色体的区域，并了解分子 有丝分裂和减数分裂期间染色体分离的机制 细胞分裂。 该赠款支持的中心粒研究被携带 使用作为实验系统出现的酵母，糖疗法 酿酒酵母和丝状真菌，曲霉尼杜兰人。 合成的 含有功能性的丝粒（CEN），DNA复制器 功能和端粒DNA（如果是线性），构成了宝贵的探针 染色体结构和功能的研究。 具体目的包括： （1）构建结构变化的Centromere DNA随改变的 功能，使用体外诱变技术； （2）指定动力学结构蛋白的基​​因的鉴定 或形成酵母动物学所必需的基因产品； （3）动力学蛋白的隔离和表征（Centromere 结合蛋白）; （4）研究动物学微管关联机理； （5）研究中心粒区的专门DNA结构， 包括复制中间体，扭结的DNA和甲基化的DNA； （6）centromere dnas的分离和结构表征 曲霉尼杜兰人，作为对Centromere的理解的一步 更复杂的生物的结构功能。 研究细胞分裂和分子机制和 在实验可触及的下真核生物中的染色体分离 提供一种理解类似机制的方法 在较高的生物体中通常和异常的功能。