Transposition and DNA Repair in Drosophila

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影响细胞的“选择”这些途径导致不同的修复DNA的最终产物。要检查的因素是断裂的基因组位置，DNA修复突变的存在，机体的年龄和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”方法已经开发了一种系统，并且可以确定四种替代途径的相对使用，DNA断裂发生在一种特别构建的名为Rf1ter1的转座遗传元件内的特定位点。不同的修复途径导致遗传上可区分的产物。为了确定基因组位置的影响，将Rreporter 1元件定位于果蝇基因组内的多个位点，并确定每个位点的四种reporter 1途径的相对使用。对于其他变量，Rreporter 1的位置是固定的，而遗传背景，个体年龄，医学意义DNA修复被认为是维持基因组稳定性的关键，特别是在具有复杂基因组的物种中。许多DNA修复基因中的人类突变，包括本研究中几个基因座的人类同源物，一些修复途径主要产生忠实的修复产物，但其他修复途径非常容易出错。因此，路径的选择对于癌症保护至关重要性能站点=======================

EXCEED THE SPACE PROVIDED 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 mganism 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 R] eporterl element is noved to a variety of sites within the Drosophila genome, and the relative usage of the four repmr pathways is ascertained for each position Fol the other variables, the positions of Rreporter 1 are fixed, while changes in the genetic backgl ound, age of the individual, or environmental vmiables are tested for their effects on pathway usage Medical Significance DNA repair is recogl]ized as c] ucial 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 ploducts, but others are highly error-prone Thus, the choice of pathway can be critical for cancer protection PERFORMANCE SITE ========================================Section End===========================================