CHROMOSOMAL TELOMERES IN DROSOPHILA

端粒是线性真核生物末端的特化区域 它们的完整性所需的染色体。DNA 在染色体DNA末端附近的一些单一的- 细胞真核生物已经被分离和鉴定，但非常 人们对DNA的相应区域知之甚少 后生动物的染色体。主要的长期目标 建议的研究是为了更好地理解：1) 果蝇染色体顶端的结构 以及这种结构是如何被调整以执行 端粒的功能；2)突变的后果 染色体顶端DNA的丢失；3) 染色体对基因表达的定位，特别是对基因的定位 移位到端粒区域。 本应用程序中建议的实验将重点放在 正常和重排末端的DNA序列组织 果蝇的染色体。三个P元件转座子携带 白色基因，每个插入在不同的 染色体，将用于：1)分离周围的端粒 利用重组DNA技术获得DNA序列；2)促进 并分析相邻的DNA重排；3)研究 异位放置在端粒中的基因的表达 环境。 在初步研究中，已经诱导了其中一个转座子 导致高频率的局部染色体重排。 携带这种重排的苍蝇很容易识别，因为 重排对白蛋白表达的影响 基因是转座子的一部分。一些重新安排 似乎是染色体末端的缺失，其中 转座子被带到染色体的最末端。 有趣的是，在随后几代苍蝇的进化过程中 最接近基因末端的转座子DNA序列 染色体逐渐丢失。

Telomeres are specialized regions at the tips of linear eukaryotic chromosomes which are required for their integrity. The DNA near the ends of the chromosomal DNA of a number of single- celled eukaryotes has been isolated and characterized, but very little is known about the corresponding regions of the DNA from the chromosomes of metazoans. The major long-term objectives of the proposed research are to better understand: 1) the structure of the tips of the chromosomes of Drosophila melanogaster and how this structure is adapted for carrying out the functions of the telomere; 2) the consequences of mutational loss of the DNA from the chromosome tip region; 3) the effect of chromosomal location on gene expression, particularly for genes translocated to the telomeric regions. The experiments proposed in this application will focus on the DNA sequence organization at the tips of normal and rearranged Drosophila chromosomes. Three P-element transposons carrying the white gene, each inserted at the tip of a different chromosome, will be used to: 1) isolate surrounding telomeric DNA sequences using recombinant DNA techniques; 2) promote and analyze adjacent DNA rearrangements; 3) study the expression of genes ectopically placed in a telomeric environment. In preliminary studies one of these transposons has been induced to cause local chromosomal rearrangements at high frequency. Flies carrying such rearrangements are easily recognized because of the effect of the rearrangement on the expression of the white gene that is part of the transposon. Some of the rearrangements appear to be terminal chromosomal deletions in which the transposon is brought to the very end of the chromosome. Interestingly, over the course of subsequent generations of flies the transposon DNA sequences closest to the end of the chromosome are gradually lost.