ENZYME SYNTHESIS AND DEGRADATION IN METABOLIC CONTROL

代谢控制中的酶合成和降解

• 批准号: 3268697
• 负责人: ROBERT T SCHIMKE
• 金额: $ 30.86万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-09-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3268697
• 关键词: cell population study; chromosome disorders; dihydrofolate reductase; drug metabolism; drug resistance; enzyme induction /repression; enzyme structure; extrachromosomal DNA; flow cytometry; genetic manipulation; genetic transcription; immunochemistry; messenger RNA; methotrexate; natural gene amplification; nucleic acid sequence; radiotracer

The overall aim of this proposal is to understand the mechanism(s) of gene amplification and chromosome rearrangements as studied with methotrexate resistance and the dihydrofolate reductase gene. We believe these processes involve two steps: 1) overreplication of DNA, 2) recombination to generate amplified genes as well as a wide variety of chromosomal aberrations- rearrangements. Our specific aims include: A: To define the molecular events that occur during the time that DNA replication is inhibited, which upon resumption result in overreplication of DNA. B: To determine the temporal relationship between transcription and replication of the dihydrofolate reductase gene. C: To determine if actively transcribed genes are more prone to amplification and constitute "hot spots" for recombination events. D: To determine if the time of replication of a gene (or DNA sequence) is related to its propensity for amplification.

该提议的总体目的是了解机制 研究的基因扩增和染色体重排 甲氨蝶呤耐药性和二氢叶酸还原酶 基因。 我们认为这些过程涉及两个步骤：1） DNA的过度复制，2）重组以产生扩增 基因以及多种染色体畸变 - 重排。 我们的具体目的包括： 答：定义在此期间发生的分子事件 DNA复制受到抑制，恢复后会导致 DNA的过度复制。 B：确定转录之间的时间关系 二氢叶酸还原酶基因的复制。 C：确定主动转录基因是否更容易 放大并构成重组事件的“热点”。 D：确定基因复制时间（或DNA）是否 序列）与其扩增的倾向有关。