DROSOPHILA CHORION GENE AMPLIFICATION

果蝇绒毛膜基因扩增

• 批准号: 2185911
• 负责人: JOHN Gerard TOWER
• 金额: $ 15.15万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2185911
• 关键词: DNA replication origin; Drosophilidae; chemical binding; developmental genetics; eukaryote; gamma radiation; gene expression; gene mutation; genetic mapping; genetic regulation; genetic transcription; genetically modified animals; messenger RNA; molecular cloning; natural gene amplification; northern blottings; nucleic acid sequence; nucleic acid structure; ovary; southern blotting; transcription factor

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.

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， 以组织特异性和时间特异性的方式调节它们的发射， 协调这一活动与附近基因的转录。 的 所使用的模型系统是发育调节放大 果蝇卵巢滤泡细胞中的绒毛膜基因簇， 展示了每一个层次的调节。 DNA复制的控制和基因扩增的现象， 与人类癌症的研究特别相关。 几个原- 癌基因和肿瘤抑制基因参与调节 DNA复制。 此外，几种肿瘤与 原癌基因的特异性扩增;和特异性基因扩增 与对化疗剂的耐药性的发展有关。 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是编码蛋白质的基因， 特异性结合顺式作用扩增调节序列， 通过表达筛选克隆。 CF2突变的表型将 进行分析，并将CF 2在扩增中的生化功能 通过将改变的CF2基因引入转基因果蝇来确定。 K43是 通过突变识别的基因，这是反式所需的 放大 K43将被克隆和测序，其生物化学作用 放大倍数也将确定。