CHROMOSOME STRUCTURE

这项提案的两个主要目标是了解 果蝇的染色体是在DNA中编码的，为了了解它是如何调控的 信号决定了转录控制的主要水平。 果蝇。与结构性问题有关的具体领域涉及 编码多线染色体的三维形态； 多线染色体与非多线染色体以及DNA区域的关系 这是在多线染色体中诱导RNA泡沫化所必需的。 与染色体转录方面有关的特定区域 功能与监管信号的时间和性质有关 果蝇的剂量补偿，以及 需要建立或失去这种补偿；监管信号 它们被叠加在RNA吞噬信号上以产生自主的 在可诱导的喷雾中对邻近基因的转录控制 区域；转录失活的机制，由 I型插入核糖体RNA基因。要使用的特定DNA序列 这些实验包括核糖体，卫星，组蛋白，双胸， 热休克蛋白基因83以及染色体47D和47D附近的序列 7楼。 实现这些目标的方法包括遗传学、细胞学、 以及分子生物学方法。胚系转化利用 P元素将为解决所提出的问题提供一个功能分析 这里。 这个项目有几个与健康有关的方面；一个潜在的 将研究致癌基因或致癌调控因子；成功 在正常情况下不是以多线为目的地的细胞中诱导多线可能 导致在哺乳动物细胞中诱导多丝分裂，这将是一种 有用的细胞遗传学进展；DNA复制的早熟激活 起源似乎在果蝇中很常见。后一种现象可能是 与看似重要的基因扩增的初始事件有关 在一些肿瘤中，以及在肿瘤细胞对某些 化疗药物。

The two broad goals of this proposal are to learn how the structure of Drosophila chromosomes is encoded in DNA, and to learn what regulatory signals determine the major levels of transcriptional control in Drosophila. The specific areas that relate to structural questions concern encoding the three-dimensional morphology of polytene chromosomes; the relationship between polytene and non-polytene chromosomes; and DNA regions that are necessary for the induction of RNA puffs in polytene chromosomes. The specific areas that relate to transcriptional aspects of chromosome function concern the timing and the nature of the regulatory signals for dosage compensation in Drosophila, and the evolutionary changes that are needed to establish or to lose this compensation; the regulatory signals that are superimposed on RNA puffing signals to result in autonomous transcriptional control of neighboring genes within an inducible puff region; the mechanism of transcriptional inactivation that is conferred by type I inserts in ribosomal RNA genes. Specific DNA sequences to be used for these experiments include ribosomal, satellite, histone, bithorax, heat-shock protein gene 83, and sequences near chromosome regions 47D and 7F. The methodology for achieving these goals includes genetic, cytological, and molecular biological approaches. Germ-line transformation using P-elements will provide a functional assay for resolving questions posed here. There are several health-related aspects of this project; a potential oncogene or regulator of oncogenesis will be studied; the successful induction of polyteny in cells not normally destined for polyteny could lead to the induction of polyteny in mammalian cells, which would be a useful cytogenetic advance; the precocious activation of DNA replication origins appears to be common in Drosophila. This latter phenomenon may be related to initial events of gene amplification that appear to be important in some tumors, and in development of resistance by tumor cells to some chemotherapeutic drugs.