Adaptive response: induced synthesis of DNA repair enzymes by alkylating agents
Adaptive response: induced synthesis of DNA repair enzymes by alkylating agents
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适应性反应：烷化剂诱导 DNA 修复酶的合成
DOI：
10.1016/0168-9525(87)90167-3
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发表时间：
1987
影响因子：
11.4
通讯作者：
Y. Nakabeppu
中科院分区：
文献类型：
--
作者：
M. Sekiguchi;Y. Nakabeppu
当大肠杆菌细胞暴露于低剂量的烷化剂时，会形成某些对 DNA 进行空气烷基化损伤的酶。这个过程被称为适应性反应，由 ada 基因控制，其产物是修复酶和转录调节因子。甲基腺嘌呤-DNA 糖基化酶 I 和 II 2-s。这两种酶可通过分子大小和酶性质来区分。糖基化酶l（分子量21000）仅纤维化3-甲基腺嘌呤，并且其活性被反应产物3-甲基腺嘌呤抑制。另一方面，糖基化酶II(分子量31400)除3-甲基腺嘌呤外，还纤维化3-甲基鸟嘌呤、7-甲基鸟嘌呤、O-甲基胸腺嘧啶和O-2-甲基胞嘧啶，且其活性不受3-甲基腺嘌呤抑制。此外，这两种酶对烷基化剂的反应不同。在暴露于低浓度烷化剂的细胞中，糖基化酶 II 的活性可增加 30 倍，而糖基化酶 I 的水平在这种处理下没有变化。已分离出这些酶有缺陷的大肠杆菌突变体：对甲基化剂中度敏感的标签突变体缺乏组成型糖基化酶 I 活性6； a/kA突变体对甲基化剂的毒性极其敏感，在用烷化剂处理后不能诱导糖基化酶II3。 4、7； tag alkA 双突变体比 alkA 突变体对甲基化剂更敏感 8。这些结果强烈表明这两种酶负责修复毒性损伤 3-甲基腺嘌呤。有证据表明 3-甲基腺嘌呤不仅会导致致命效应，还会导致突变和 SOS 诱导。克隆了 tag 和 alkA 基因，并
Certain enzymes that r@ air alkylation lesions in DNA are formed when Escherichia coil cells are exposed to low d~ ses of alkylating agents. This process, termed the adaptive response, is controlled by the ada gene, whose product is a rePair enzyme as well as a transcriptional regulator. methyladenlne-DNA glycosylase I and II 2-s. The two enzymes are distinguishable by both molecular size and enzymatic properties. Glycosylase l (molecular weight 21000) fiberates only 3-methyladenine, and the activity is inhibited by the reaction product, 3-methyladenine. On the other hand, glycosylase II (molecular weight 31400) fiberates 3-methylguanine, 7-methylguanine, O~-methylthymine and 02-methylcytosine in addition to 3-methyladenine, and the activity is not inhibited by 3-methyladenine. Moreover, the two enzymes differ in their response to aikylafing agents. The activity of glycosylase II can be increased 30-fold in cells exposed to low concentrations of alkylating agents, whereas the level of glycosylase I is unchanged by such treatments. Mutants of E. coil that are defective in these enzymes have been isolated: tag mutants, which are moderately sensitive to methylating agents, are deficient in the constitutive glycosylase I activity6; a/kA mutants, which are extremely sensitive to the toxicity of methyiating agents, cannot induce glycosylase II after treatment with alkylating agents3. 4, 7; tag alkA double mutants are more sensitive to methylating agents than are alkA mutants 8. These results strongly suggest that both of these enzymes are responsible for repair of the toxic lesion, 3-methyladenine. There is evidence that 3-methyladenine causes not only lethal effects but also mutation and SOS induction. The tag and alkA genes were cloned, and their