STRUCTURE AND FUNCTION OF TELOMERES

端粒的结构和功能

• 批准号: 2734406
• 负责人: ELIZABETH H BLACKBURN
• 金额: $ 39.29万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734406
• 关键词: DNA binding protein; DNA footprinting; DNA replication; Tetrahymena; Trypanosoma; X ray crystallography; Xenopus; affinity chromatography; alternatives to animals in research; binding proteins; chromosomes; circular dichroism; covalent bond; enzyme mechanism; eukaryote; gel electrophoresis; genetic manipulation; genetic recombination; genome; microorganism genetics; molecular cloning; nucleic acid sequence; nucleic acid structure; protein biosynthesis; protein structure function; ribosomal RNA; telomerase; telomere

The aim of the research in this proposal is to understand the mechanisms of telomere function in eukaryotes. Telomeres are essential chromosomal elements which stabilize the ends of linear nuclear chromosomes and allow their complete replication. Much of the proposed work emphasizes the ciliated protozoans Tetrahymena and Euplotes, which, because of specific aspects of their biology, afford advantageous experimental systems for study of telomere, function. Telomere structure is highly conserved throughout eukaryotes, and findings made in one system are likely to be relevant to general questions of telomere function. Specific aims are to 1) determine the function of the essential RNA of a novel ribonucleoprotein enzyme, telomerase, that synthesizes the G-rich strand of the simple repeated sequences that form the essential cis-acting components of telomeres, 2) determine what structural features of telomeric DNA are required for recognition by telomerase, and investigate the mechanism of de novo telomere formation that occurs in ciliate macronuclear differentiation and chromosome healing, 3) investigate the enzymes responsible for synthesis of the complementary C-rich telomeric strand. 4) study the mechanism of genomic rearrangements in ciliate development, using an in vitro reaction system we have developed.

本提案研究的目的是了解 真核生物中的端粒功能。端粒是染色体所必需的 稳定线性核染色体末端并允许 他们的完整复制。大部分拟议的工作都强调 纤毛原生动物四膜虫和游标虫，由于特定的 他们的生物学方面，提供有利的实验系统 端粒、功能的研究。 端粒结构高度保守 在整个真核生物中，在一个系统中取得的发现很可能是 与端粒功能的一般问题相关。具体目标是 1) 确定新型核糖核蛋白必需 RNA 的功能 端粒酶，合成简单的富含G链 形成基本顺式作用成分的重复序列 端粒，2) 确定端粒 DNA 的结构特征 端粒酶识别所需的分子，并研究端粒酶识别的机制 纤毛虫大核分化中发生的新端粒形成 和染色体愈合，3）研究负责的酶 互补的富含C端粒链的合成。 4）研究 纤毛虫发育中基因组重排的机制 我们拥有的体外反应系统 发达。