CHROMOSOME STRUCTURE AND FUNCTION

本提案的两个主要目标是了解 果蝇的染色体编码在DNA中，为了了解 信号决定转录控制的主要水平， 果蝇 与结构问题有关的具体领域包括： 编码多线染色体的三维形态; 多线染色体和非多线染色体之间的关系;以及DNA区域 这是在多线染色体中诱导RNA泡芙所必需的。 与染色体转录相关的特定区域 功能涉及调节信号的时间和性质， 果蝇的剂量补偿，以及 需要建立或失去这种补偿;监管信号 这些信号叠加在RNA膨胀信号上， 可诱导喷流内邻近基因的转录控制 区域;转录失活的机制，这是赋予 I型插入核糖体RNA基因。 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，以及染色体区域47 D附近的序列， 7楼 实现这些目标的方法包括遗传学，细胞学， 和分子生物学方法。 生殖系转化， P元素将提供一个功能分析，以解决所提出的问题 这里. 该项目有几个与健康有关的方面;一个潜在的 将研究癌基因或肿瘤发生的调节因子;成功的 在通常不具有多线性细胞中诱导多线性可 导致哺乳动物细胞中多线性的诱导，这将是一个 有用的细胞遗传学进展; DNA复制的过早激活 在果蝇中似乎很常见。 这种现象可能是 与基因扩增的初始事件有关， 在某些肿瘤中，以及肿瘤细胞对某些肿瘤产生耐药性 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.