Transposition and DNA Repair in Drosophila

超过目标提供的空间修复DNA双链断裂将在果蝇研究这项工作的目的是确定哪些因素影响细胞的“选择”的几种修复途径利用这些途径导致不同的DNA修复的因素是最终产品检验基因组的位置打破的DNA修复DNA的突变mganism的年龄和时间休息的存在大量的优惠m细胞基因”的主人已经开发出一种系统，在果蝇种系中双链断裂，并且可以确定四种替代途径的相对使用，DNA断裂发生在一个特殊构造的转座遗传元件Rreporterl内的特定位点，该元件被设计成不同的修复途径导致遗传上可区分的产物。报告因子R]被转移到果蝇基因组的不同位置，并且确定了每个位置的四种repr通路的相对使用情况。在其他变量中，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对通路使用的影响进行了测试。特别是在具有复杂基因组的物种中，许多DNA修复基因的人类突变，包括本研究中几个基因座的人类同源基因，导致癌症易感性。一些修复途径主要产生忠实的修复产物，但其他修复途径极易出错，因此，途径的选择对癌症保护至关重要

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===========================================