GENETIC CONTROL OF MUTATION IN DROSOPHILA

该项目旨在确定DNA之间的关系 果蝇的染色体修复、染色体结构和诱变 黑腹菌 增加突变频率的突变（a 突变体）已经被鉴定和表征。 变种人大大 降低了修复X射线诱导的染色体断裂的效率， 卵母细胞，从而允许以前未描述的修复途径， 观察 通过这种新发现的修复途径， 末端被新的端粒“封端”。 新的染色体末端是 保护免于降解，但不能有效复制; DNA 序列从加帽末端丢失。 的拟稳定导数 封端已被分离，并发现已获得 端粒特异性DNA序列，称为HeT，其具有以下结构 类似于反转录转座子 初步证据显示， 由于DNA不完整，自然染色体末端也会后退 复制和偶尔延长收购HeT。 的 损失率由换位率平衡，以保持 染色体长度 我们还在开发一种快速检测方法， 促进遗传分析和研究细胞的增变因子 mutator活性的特异性。 突变基因已经被定位到 染色体区域62 B12-C1使用150个缺失的嵌套组。 一 跨越该区域的酵母人工染色体已被亚克隆， 映射删除断点的位置，并识别 对应于突变基因的转录单位。

This project is designed to determine the relationships among DNA repair, chromosome structure and mutagenesis in Drosophila melanogaster. A mutation that increases the mutant frequency (a mutator) has been identified and characterized. The mutator greatly reduces the efficacy of repair of x-ray-induced chromosome breaks in oocytes, thereby allowing a previously undescribed repair pathway to be observed. By this newly identified repair pathway broken chromosome ends are "capped" with a new telomere. The new chromosome ends are protected from degradation, but are not replicated effectively; DNA sequences are lost from the capped ends. Quasi-stable derivatives of the capped ends have been isolated and found to have gained a telomere-specific DNA sequence, termed HeT, which has a structure resembling a retrotransposon. Preliminary evidence suggests that natural chromosome ends also recede because of incomplete DNA replication and occasionally lengthen by the acquisition of HeT. The rate of loss is balanced by the rate of transposition to maintain chromosome length. We are also developing a rapid assay for the mutator to facilitate genetic analysis and investigating cell specificity of mutator activity. The mutator gene has been mapped to chromosome region 62B12-C1 using a nested set of 150 deletions. A yeast artificial chromosome that spans the region has been subcloned to map the location of the deletion breakpoints and to identify a transcription unit that corresponds to the mutator gene.