Transposition and DNA Repair in Drosophila

果蝇的转座和 DNA 修复

• 批准号: 6580024
• 负责人: William R. ENGELS
• 金额: $ 46.07万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6580024
• 关键词: DNA damage; DNA repair; Drosophilidae; gene expression; gene mutation; genetic screening; green fluorescent proteins; polymerase chain reaction; site directed mutagenesis; transposon /insertion element

DESCRIPTION (provided by applicant): Goals: The repair of double-strand DNA breaks will be studied in Drosophila This work is aimed at determining what factors influence the cell's "choice" of which of several repair pathways to utilize These pathways lead to different final products of repaired DNA The factors to be examined are: Genomic position of break Presence of DNA repair mutations Age of the organism and timing of the DNA break The existence of a large number of breaks m the cell Genetic "master switches" that affect gene expression Methods: A system has been developed whereby double-strand breaks are made in the Drosophila germline, and the relative usage of four alternative pathways can be ascertained DNA breakage occurs at a particular site within a specially constructed transposable genetic element named Rreporterl The element is designed in such a way that the different repair pathways lead to genetically distinguishable products To determine the effect of genomic position, the Rreporter I element is moved to a variety of sites within the Drosophila genome, and the relative usage of the four repair pathways is ascertained for each position. For the other variables, the positions of Rreporter 1 are fixed, while changes in the genetic background, age of the individual, or environmental variables are tested for their effects on pathway usage Medical Significance: DNA repair is recognized as crucial to maintaining the stability of the genome, especially in species with complex genomes Human mutations in many DNA repair genes, including the human homologs of several of the loci in the present study, cause predisposition to cancer Some of the repair pathways produce primarily faithful repair products, but others are highly error-prone Thus, the choice of pathway can be critical for cancer protection

描述（由申请人提供）： 目标：将在果蝇中研究双链DNA断裂的修复，这项工作旨在确定哪些因素会影响细胞的“选择”，即使用这些途径的几种维修途径中哪些的“选择”导致修复后的DNA的不同最终产物。 断裂基因组位置 DNA修复突变的存在 生物的年龄和DNA断裂的时间 细胞中存在大量断裂 影响基因表达的遗传“主开关” 方法：已经开发了一个系统，在果蝇种系中进行双重断裂，并且可以确定四个替代途径的相对用法可确定DNA断裂发生在一个特定构造的可旋转遗传元素内的特定地点，该遗传元素被称为rreporterl rreporterl rreporterl rreporterl的元素以这种方式使元素具有不同的元素，从而使遗传的元素差异化，以确定遗传的遗传效果。每个位置都确定了果蝇基因组中的位点以及四个修复途径的相对用法。对于其他变量，rreporter 1的位置是固定的，而遗传背景，个体年龄或环境变量的变化都对其对途径使用的影响进行了测试 医学意义：DNA修复对于维持基因组的稳定性至关重要，尤其是在许多DNA修复基因中具有复杂基因组突变的物种中，包括本研究中几个基因座的人类同源物，使癌症的易感性易于癌症，因此一些忠实的修复产物可能会产生重要的癌症，因此，癌症是很重要的，因此，癌症是重要的。