GENETIC BEHAVIOR OF REPEATED SEQUENCES

重复序列的遗传行为

• 批准号: 2175814
• 负责人: Hannah L. Klein
• 金额: $ 31.17万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-05-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2175814
• 关键词: DNA repair; Saccharomyces cerevisiae; fungal genetics; gene complementation; gene conversion; gene duplication; gene expression; gene mutation; genetic crossing over; genetic markers; genetic recombination; meiosis; molecular cloning; nucleic acid sequence; radiation genetics; suppressor mutations

The long-term objectives are to understand the genetic and molecular regulation of genome stability and DNA recombination. Mitotic recombination occurs primarily in response to DNA damage and can directly repair DNA damage. Recombination between repeated sequences is important for both generating and maintaining sequence diversity. Recombination between repeats must be regulated as it has the potential to cause lethal rearrangements. Recombination between repeats is recognized as an important mechanism of mutation in human diseases and is correlated with tumor growth. The genetic regulation of mitotic recombination will be studied using Saccharomyces cerevisiae as a model system. The proposed experiments investigate the number of pathways of mitotic recombination between repeats. The specific aims of the proposal are: 1) An examination of the role of RAD genes which are involved in DNA repair in specific recombination events in mitosis. 2) Characterization of novel mutants which suppress mitotic recombination. 3) Examination of the molecular events in repeat recombination using a substrate to test different models of pairing in double-strand break stimulated recombination. 4) Study of the role of the excision repair gene RAD1 in meiotic recombination. 5) Study of novel mutations that are synthetically lethal in a hpr1 strain to identity genes involved in mitotic recombination. 6) Purity and characterize the biochemical activities of the HPR1 protein. Absence of the HPR1 protein results in increased mitotic recombination.

长期目标是了解遗传和分子 调节基因组稳定性和DNA重组。有丝分裂 重组主要是响应DNA损伤而发生的，并且可以直接 修复DNA损伤。重复序列之间的重组很重要 用于产生和维持序列多样性。重组 重复之间必须调节，因为它具有引起致命的潜力 重排。重复之间的重组被认为是 人类疾病中突变的重要机制，与 肿瘤生长。 将研究有丝分裂重组的遗传调节 酿酒酵母作为模型系统。提出的实验 研究有丝分裂重组的途径数量 重复。该提案的具体目的是： 1）检查参与DNA的RAD基因的作用 修复有丝分裂的特定重组事件。 2）抑制有丝分裂的新型突变体的表征 重组。 3）使用A重复重组中的分子事件检查 底物以双链中断测试不同模型的配对模型 刺激重组。 4）研究切除修复基因rad1在减数分裂中的作用 重组。 5）研究HPR1中合成致命的新型突变 与有丝分裂重组有关的身份基因的菌株。 6）纯度和表征HPR1的生化活动 蛋白质。缺乏HPR1蛋白会导致有丝分裂增加 重组。