Transient inhibition of DNA synthesis results in increased dihydrofolate reductase synthesis and subsequent increased DNA content per cell.
Transient inhibition of DNA synthesis results in increased dihydrofolate reductase synthesis and subsequent increased DNA content per cell.
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DNA 合成的瞬时抑制导致二氢叶酸还原酶合成增加，随后每个细胞的 DNA 含量增加。
DOI：
10.1128/mcb.6.10.3373-3381.1986
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发表时间：
1986
影响因子：
5.3
通讯作者：
Schimke,RT
中科院分区：
文献类型：
--
作者：
Johnston,RN;Feder,J;Hill,AB;Sherwood,SW;Schimke,RT
我们研究了细胞周期中细胞的阻断在刺激基因扩增和增强耐药性中可能发挥的作用。我们发现，几种不同的抑制剂的DNA合成，这是每一个都能够阻止细胞在G1-S期边界，诱导增强环己酰亚胺敏感的合成早期S期细胞周期调节酶，二氢叶酸还原酶，以及其他蛋白质。这种反应是特异性的，因为在G2期的阻断不会导致酶的过量产生。当细胞从药物抑制中释放时，DNA合成恢复，导致每个细胞的DNA含量对环己酰亚胺敏感性升高。我们推测，过量的DNA合成（这可能有助于后来可检测到的基因扩增事件）是受影响细胞中S期特异性蛋白质积累的结果，然后可能会影响DNA复制的模式。
We examined the role that blockage of cells in the cell cycle may play in the stimulation of gene amplification and enhancement of drug resistance. We found that several different inhibitors of DNA synthesis, which were each able to block cells at the G1-S-phase boundary, induced an enhanced cycloheximide-sensitive synthesis of an early S-phase cell cycle-regulated enzyme, dihydrofolate reductase, and of other proteins as well. This response was specific, in that blockage at the G2phase did not result in overproduction of the enzyme. When the cells were released from drug inhibition, DNA synthesis resumed, resulting in a cycloheximide-sensitive elevation in DNA content per cell. We speculate that the excess DNA synthesis (which could contribute to events detectable later as gene amplification) is a consequence of the accumulation of S-phase-specific proteins in the affected cells, which may then secondarily influence the pattern of DNA replication.