Healing of Broken Eucaryotic Chromosomes

修复断裂的真核染色体

• 批准号: 8711517
• 负责人: James Haber
• 金额: $ 35.02万
• 依托单位: Brandeis University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-11-15 至 1991-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8711517&HistoricalAwards=false
• 关键词: Healing; Broken; Eucaryotic; Chromosomes

Telomeres, specialized structures at chromosome ends, are essential to maintain chromosome stability. Broken chromosomes are unstable, but may become "healed" by recombination with an intact homologue, or by more novel means to produce terminally deficient chromosomes. These may arise either by de novo telomere formation or by translocations. A detailed analysis of chromosome repair will be carried out in the yeast Saccharomyces Cerevisiae, using several methods to introduce chromosome breaksat one chromosomal location. Strains containing de novo telemeres will be analyzed to determine the molecular mechaniswm by which these ends are added to broken chromosomes. Translocations will be monitored by an improved method of detection. We have discovered a novel form of repair of broken chromosomes, by recombination between homologous regions well-separated from, but flanking the break-point. This intra-chromosomal repair system will be analyzed in detail, to determine how far homologous sites can be separated and how much homology is required. This event can be induced synchronously and followed in "real time" by DNA analysis. Special emphasis will be given to understanding the mechanism by which broken chromosomes become shorter. The structure of normal telomeres will also be examined to determine the origin of a high degree of polymorphism and rearrangement in the regions immediately adjacent to telomeres. Finally, we will extend our study of the repair of broken chromosomes to another, evolutionarily divergent yeast, Schizosaccharomyces cerevisiae. Linear dicentric chromosomes will be generated by meiotic recombination between a linear chromosome and a circular chromosome constructed by recombinant DNA techniques. The differences in chromosome structure and DNA repair mechanisms between S. pombe and S. cerevisiae are expected to reveal different types of healing events. Little is known of chromosome structure and how it is maintained. The stability of chromosomes which allows faithful segregation must be inherent in the structure and this work will provide insight into that structure.

端粒是染色体末端的特化结构， 对维持染色体稳定性至关重要。 破碎 染色体是不稳定的，但可能会被“治愈”， 与完整同源物的重组，或通过更新颖的 意味着产生终末缺陷染色体。 这些可以 由端粒从头形成或由 易位 染色体修复的详细分析 将在酿酒酵母中进行， 采用多种方法引入染色体断裂 染色体定位 含有新发端粒的菌株 将进行分析，以确定分子机制， 这些末端被添加到断裂的染色体上。 易位将通过一种改进的方法进行监测， 侦测 我们发现了一种新的修复方法 断裂的染色体，通过同源染色体之间的重组 与断裂点分开但位于断裂点两侧的区域。 这种染色体内修复系统将在 细节，以确定同源位点可以有多远， 分离以及需要多少同源性。 此事件可 被DNA“真实的时间”同步诱导和跟随 分析. 将特别强调理解 断裂的染色体变短的机制。 正常端粒的结构也将被检查， 确定高度多态性的起源， 在紧邻的区域重新排列 端粒 最后，我们将扩展我们的研究修复 断裂的染色体到另一个进化上不同的 酵母，酿酒裂殖酵母。 线状双着丝粒的 染色体将通过减数分裂重组产生 线性染色体和环形染色体之间的区别 通过重组DNA技术构建。 的差异 在染色体结构和DNA修复机制方面的研究。 pombe和S.酿酒酵母有望揭示不同的 治疗事件的类型。 我们对染色体的结构和它是如何形成的知之甚少 树立政治意识 染色体的稳定性使得 忠实的隔离必须是结构中固有的， 这项工作将使人们深入了解这一结构。