CHROMOSOMAL TELOMERES IN DROSOPHILA

端粒是真核生物染色体末端的特化区域， 染色体的完整性所必需的。 的DNA 在染色体DNA的末端附近， 细胞真核生物已被分离和表征，但非常 对于来自于人类的DNA的相应区域知之甚少， 后生动物的染色体 主要长期目标 建议的研究是为了更好地了解：1） 果蝇染色体顶端的结构 以及这种结构如何适合于执行 端粒的功能; 2）突变的后果 染色体末端DNA的丢失; 3） 基因表达的染色体定位，特别是对于基因 转移到端粒区。 在本申请中提出的实验将集中于 DNA序列组织在正常和重排的尖端 果蝇染色体。 三个P元件转座子携带 白色基因，每一个都插入到不同的 染色体，将用于：1）分离周围端粒 使用重组DNA技术的DNA序列; 2）促进 并分析邻近的DNA重排; 3）研究 异位放置在端粒中的基因的表达 环境 在初步的研究中，这些转座子中的一个已经被诱导 导致局部染色体高频率重排。 携带这种重排的苍蝇很容易被识别， 重组对白色表达的影响 是转座子的一部分 一些重新安排 似乎是末端染色体缺失， 转座子被带到染色体的最末端。 有趣的是，在果蝇的后代中， 最接近转座子末端的转座子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.