MECHANISMS AND REGULATION OF GENE EXPRESSION

基因表达的机制和调控

• 批准号: 3484141
• 负责人: PAUL BERG
• 金额: $ 42.75万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-09-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3484141
• 关键词: DNA replication; Drosophilidae; Escherichia coli; Polyomavirus; Primates; RNA biosynthesis; RNA splicing; UTP hexose 1 phosphate uridylyltransferase; bacterial genetics; carcinogenesis; electron microscopy; eukaryote; galactosemias; gene expression; gene induction /repression; genetic manipulation; genetic mapping; genetic recombination; genetic regulation; genetic translation; human genetic material tag; human tissue; laboratory rabbit; laboratory rat; messenger RNA; molecular cloning; mutant; nucleic acid hybridization; nucleic acid sequence; nucleoproteins; oncogenic virus; protein biosynthesis; proteins; recombinant DNA; simian virus 40; tissue /cell culture; virus DNA; virus genetics; virus replication

The advent and widespread application of the recombinant DNA methodology during the past twelve years has greatly extended our understanding of the molecular basis of heredity. More significantly, the emergence of a new molecular paradigm - reverse genetics, which relies on the ability to specifically modify the structure of genes in vitro and to test their biological properties, has revolutionized the experimental approaches in molecular genetics. The ability to construct minichromosomes with novel arrangements of genetic elements also provides vectors for the isolation of genes as well as substrates for the analysis of specific genetic reactions. Our proposal, which applies this approach to explore the basic mechanisms of gene regulation in the establishment of immune responsiveness and of genetic recombination, aims (1) identify the factors and mechanisms that limit the epression of antibody genes to only lymphoid cells; (2) isolate and characterize the human gene whose dysfunction is responsible for galactosemia; (3) understand the mechanisms responsible for non- homologous, homologous and non-reciprocal modes of genetic recombination, especially those which permit the rejoining of broken DNA; (4) develop genetic approaches to effect a replacement or repair of chromosomal DNA sequences; (5) developing vectors which can deliver genes to only specific types of cells. It is anticipated that the information we develop will advance our unerstanding of the molecular basis of disease and provide novel approaches to their prevention, treatment and cure.

重组DNA的出现和广泛应用 过去十二年的方法论已经大大扩展 我们对遗传的分子基础的理解。 更多的 值得注意的是，一种新的分子范式的出现—— 反向遗传学，依赖于特异性修饰的能力 体外基因结构并测试其生物学 性质，彻底改变了实验方法 分子遗传学。 构建微型染色体的能力 遗传元件的新颖排列还提供了 用于分离基因的载体以及基因的底物 特定遗传反应的分析。 我们的建议适用 这种方法探索基因调控的基本机制 建立免疫反应和遗传 重组、目标 (1) 找出限制因素和机制 仅对淋巴细胞表达抗体基因； (2) 分离并表征人类基因 功能障碍是半乳糖血症的原因； (3) 了解造成非正常现象的机制 同源、同源和非互易模式 基因重组，特别是那些允许 断裂DNA的重新连接； (4) 开发遗传方法来实现替代或 修复染色体DNA序列； (5) 开发能够将基因仅传递给 特定类型的细胞。 预计我们开发的信息将推进我们的 了解疾病的分子基础并提供新的 预防、治疗和治愈的方法。