ENZYME SYNTHESIS AND DEGRADATION IN METABOLIC CONTROL

这项建议的总体目的是为了理解机制(S) 基因扩增和染色体重排的研究 对甲氨蝶呤耐药和二氢叶酸还原酶 吉恩。我们认为这些过程包括两个步骤：1) DNA的过度复制，2)重组以产生扩增产物 基因以及各种各样的染色体异常- 重新安排。 我们的具体目标包括： 答：为了定义在这段时间内发生的分子事件 DNA复制被抑制，这在恢复时会导致 DNA的过度复制。 B：确定转录之间的时间关系 和二氢叶酸还原酶基因的复制。 C：确定活跃转录的基因是否更容易 并构成重组事件的“热点”。 D：确定一个基因(或DNA)的复制时间 序列)与其扩增倾向有关。

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.