NOVEL HOST GENES AFFECTING TRANSPOSITION

了解逆转录病毒的机制对医学界很有意义。 社区和普通公众，因为病毒在 感染(如艾滋病毒和其他T细胞病毒)和导致的癌症 来自原癌基因的转移和错误调控。拟议中的项目 是为了识别参与转座周期的酵母基因 酵母反转录元件Ty1。Ty1元素通过机械轴承进行换位 与感染较大真核生物的逆转录病毒有许多相似之处。Ty1是 一个很好的模型系统，因为对Ty1转座途径的剖析是 这得益于酵母分子遗传技术的简便性。 已知Ty1的转座对温度敏感。最直接的 该项目的目标是确定温度对温度的影响 转座过程，并克隆突变的酵母基因，使 在较高温度下发生换位。的长期目标是 该项目将确定这些克隆的宿主基因的功能 在换位过程中。Ty1的比较生化研究 从突变型和野生型毒株中分离的病毒样颗粒(VLP) 将能够确定它们在转位中的作用。如果 克隆的基因以前没有被研究过，遗传学研究将被 启动以确定基因的细胞功能。长期的 此建议书期限后的目标将是确定 在较大的真核生物中克隆的部分基因。这将给我们提供一些线索 病毒如何利用宿主基因，并最终可能允许战略 病毒生命周期的干扰。

An understanding of retroviral mechanisms is of interest to the medical community and the general public, because of the role of viruses in infections (such a HIV and other T-cell viruses) and cancer that result from transfer and misregulation of proto-oncogenes. The proposed project is to identify yeast genes involved in the transposition cycle of the yeast retroelement Ty1. The Ty1 element transposes via a mechanism bearing many similarities to retroviruses which infect larger eukaryotes. Ty1 is a good model system, as dissection of the Ty1 transposition pathway is facilitated by the ease of yeast molecular genetic techniques. Transposition of Ty1 is known to be temperature sensitive. The immediate goals of this project are to determine the effects of temperature on the transposition process, and to clone mutant yeast genes which allow transposition to occur at elevated temperatures. The long-term goal for the project will be to determine the function of these cloned host genes in the transposition process. Comparative biochemical studies of Ty1 virus-like particles (VLPs) isolated from mutant and wild-type strains will enable the determination of their role in transposition. If the cloned genes have not been previously studied, genetic studies will be initiated to determine the cellular function of the genes. Long-term objectives beyond this proposal period will be to identify the counter- parts of the cloned genes in larger eukaryotes. This will give clues as to how viruses utilize host genes and may eventually allow for strategic interference of viral life-cycles.