DROSOPHILA CHORION GENE AMPLIFICATION

我们研究的长期目标是了解 真核细胞将DNA的某些区域指定为复制起点， 以特定于组织和时间的方式调节它们的发射，以及 使这一活动与附近基因的转录相协调。这个 正在使用的模型系统是发育调节的扩增 果蝇卵巢卵泡细胞中的绒毛膜基因簇 展示了这些监管级别中的每一个。 DNA复制的控制，基因扩增的现象， 与人类癌症的研究特别相关。几个原型- 癌基因和抑癌基因参与肿瘤的调控。 DNA复制。此外，几种肿瘤与 原癌基因特异性扩增和特异性基因扩增 与化疗药物耐药性的形成有关。 开始了解绒毛膜基因扩增的反式作用因子 正在被克隆和分析。CF2是一种编码一种蛋白质的基因 与顺式作用的扩增调控序列特异性结合， 通过表达筛选克隆了该基因。CF2突变的表型将 检测了CF2在扩增过程中的生化功能 通过将改变的CF2基因引入转基因果蝇来确定。K43是 一种由突变识别的基因，这是反式基因所必需的 放大。K43将被克隆和测序，及其生化作用 放大倍数也将被确定。

The long term objective of our research is to understand how the eukaryotic cell designates certain regions of DNA as replication origins, regulates their firing in a tissue- and temporal-specific manner, and coordinates this activity with the transcription of nearby genes. The model system being utilized is the developmentally regulated amplification of the chorion gene clusters in Drosophila ovarian follicle cells, which exhibits each of these levels of regulation. The control of DNA replication, and the phenomenon of gene amplification, are particularly relevant to the study of human cancers. Several proto- oncogenes and tumor-suppressor genes are implicated in the regulation of DNA replication. Moreover, several tumors are associated with the specific amplification of proto-oncogenes; and specific gene amplification is implicated in the development of resistance to chemotherapeutic agents. To begin to understand chorion gene amplification the trans-acting factors are being cloned and analyzed. CF2 is a gene encoding a protein which binds specifically to cis-acting amplification regulatory sequences, which was cloned by expression screening. The phenotype of CF2 mutations will be assayed, and the biochemical function of CF2 in amplification will be determined by introducing altered CF2 genes into transgenic flies. K43 is a gene identified by mutations, which is required in trans for amplification. K43 will be cloned and sequenced, and its biochemical role in amplification will also be determined.