DNA Double Strand Break Repair in Drosophila Melanogaste

果蝇 DNA 双链断裂修复

• 批准号: 7291816
• 负责人: YIKANG RONG
• 金额: --
• 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/7291816
• 关键词: DNA; Double; Strand; Break; Repair

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Melanogaster是现代生物学大量研究领域的最佳遗传模型生物之一。然而，果蝇最有用的遗传工具之一是缺少的，即能够通过同源重组靶向特定基因进行突变。基因靶向已有二十多年了，允许酵母和小鼠研究人员将特定的突变引入基本上任何基因。这种工具对于具有完全测序基因组的生物体的基因功能研究尤其重要。 Rong博士是果蝇近期开发基因靶向方法的主要驱动力。这种方法使全世界的果蝇研究人员成功地突变了许多不同的基因座，这些基因座先前在传统突变筛选中尚未鉴定。为了证明该方法的一般适用性，Rong博士与杰拉尔德·鲁宾（Gerald Rubin）的小组合作，淘汰了肿瘤抑制p53的果蝇同源物。果蝇突变体突变表型的表征正在进行中。为了促进这项研究，Rong博士将特定于地点的双链断系统引入了果蝇中，其中人们可以控制破裂的位置，断裂的数量，断裂时间以及围绕破裂的基因组环境。使用该系统，Rong博士能够提供证据表明，DNA破裂周围的基因组结构不仅决定了修复机制，还决定了修复模板的选择。实验室的一个目标是结合位点特异性断裂系统的功率和基因靶向方法，以阐明与这些DNA病变修复有关的基因产物的功能。 Rong博士小组的工作将有助于更好地理解真核生物如何保持其基因组的身体完整性。