DNA Double Strand Break Repair in Drosophila Melanogaster

果蝇 DNA 双链断裂修复

• 批准号: 7592704
• 负责人: YIKANG RONG
• 金额: $ 97.5万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592704
• 关键词: Animal Model; Area; Ataxia-Telangiectasia-Mutated protein kinase; Biology; Collaborations; Complex; DNA; DNA Double Strand Break; DNA lesion; Development; Double Strand Break Repair; Drosophila genus; Drosophila melanogaster; Environment; Eukaryotic Cell; Gene Mutation; Gene Targeting; Genes; Genetic; Genome; Genomics; Goals; Homologous Gene; Knock-out; Methods; Mus; Mutate; Mutation; Numbers; Organism; Phenotype; Positioning Attribute; Process; Protein p53; Proteins; Research; Research Personnel; Role; Site; Structure; System; Telomere Maintenance; Time; Work; Yeasts; driving force; gene function; genome sequencing; homologous recombination; interest; mutant; repaired; tool

The fruitfly Drosophila melanogaster is one of the best genetic model organisms for a large number of research areas in modern biology. However , one of the most useful genetic tools has been prominently missing for Drosophila, that is the ability to target specific genes for mutation by homologous recombination. Gene targeting has, for over twenty years, allowed yeast and mouse researchers to introduce specific mutations to essentially any gene. Such a tool is especially important for gene function studies in organisms with a completely sequenced genome. Dr. Rong was the main driving force for the recent development of a gene targeting method in Drosophila. Such method has allowed Drosophila researchers worldwide to successfully mutate many different loci that were not previously identified in traditional mutant screens. As a demonstration of the general applicability of the method, Dr. Rong knocked out the Drosophila homolog of the tumor suppressor p53 in collaboration with Dr. Gerald Rubin's group. Characterization of the mutant phenotype of the Drosophila mutant is in progress. The main research interest of Dr. Rong's group is to study the mechanisms for DNA double strand break repair in Drosophila. To facilitate such a study, Dr. Rong has introduced a site-specific double strand break system into Drosophila in which one can control the position of the break, the number of breaks, the timing of breakage, and the genomic environment surrounding the break. Using this system, Dr. Rong was able to provide evidence suggesting that genomic structure around the DNA break dictates the choice of not only the repair mechanism but also the template for repair. A goal of the lab is to combine the power of the site-specific breakage system and the gene targeting method to elucidate the function of gene products involved in the repair of these DNA lesions. The work of Dr. Rong's group would contribute to a better understanding of how eukaryotic organisms maintain the physical integrity of their genomes.

果蝇果蝇是现代生物学众多研究领域的最佳遗传模型生物之一。然而，果蝇明显缺乏最有用的遗传工具之一，即通过同源重组靶向特定基因进行突变的能力。二十多年来，基因打靶使酵母和小鼠研究人员能够向几乎任何基因引入特定突变。这种工具对于具有完整基因组测序的生物体的基因功能研究尤其重要。荣博士是最近开发果蝇基因打靶方法的主要推动者。这种方法使世界各地的果蝇研究人员能够成功地突变许多以前在传统突变筛选中未发现的不同基因座。为了证明该方法的普遍适用性，Rong 博士与 Gerald Rubin 博士的团队合作敲除了肿瘤抑制因子 p53 的果蝇同源物。果蝇突变体的突变表型的表征正在进行中。荣博士课题组的主要研究兴趣是研究果蝇DNA双链断裂修复机制。为了促进这项研究，荣博士将一种位点特异性双链断裂系统引入果蝇中，在该系统中，人们可以控制断裂的位置、断裂的数量、断裂的时间以及断裂周围的基因组环境。使用该系统，Rong 博士能够提供证据表明 DNA 断裂周围的基因组结构不仅决定了修复机制的选择，还决定了修复模板的选择。该实验室的目标是将位点特异性断裂系统的力量与基因靶向方法结合起来，阐明参与修复这些 DNA 损伤的基因产物的功能。荣博士小组的工作将有助于更好地了解真核生物如何保持其基因组的物理完整性。