A region of the Ada DNA-repair protein required for the activation of ada transcription is not necessary for activation of alkA.
A region of the Ada DNA-repair protein required for the activation of ada transcription is not necessary for activation of alkA.
复制标题
ada 转录激活所需的 Ada DNA 修复蛋白区域对于 alkA 的激活不是必需的。
DOI：
10.1073/pnas.88.20.9001
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发表时间：
1991
影响因子：
11.1
通讯作者：
Walker,GC
中科院分区：
文献类型：
--
作者：
Shevell,DE;Walker,GC
大肠杆菌的适应性反应保护细胞免受烷化剂的诱变和毒性作用。这种反应由Ada蛋白控制，Ada蛋白不仅作为ada和alkA基因的转录激活因子发挥作用，而且还具有两种DNA甲基转移酶活性。Ada通过将甲基从DNA甲基磷酸三酯转移到其自身的Cys-69残基上，然后结合到存在于Ada和alkA启动子中的DNA序列（Ada盒），从而转化为有效的转录激活因子。虽然Ada蛋白最初似乎以类似的方式调节Ada和alkA基因，但我们的研究表明，野生型Ada蛋白及其截短衍生物可以差异调节Ada和alkA转录。在体内，激活ada转录所需的野生型甲基化Ada水平低于alkA转录。在暴露于烷化剂的细胞中，含有DNA结合结构域的Ada的N-末端半部分足以有效激活alkA转录，但不足以激活ada转录。此外，含有80-90%的Ada的截短衍生物是非常强的Ada组成型激活剂，但仅是alkA转录的诱导型激活剂。这些结果表明，Ada激活Ada转录的机制不同于它激活alkA转录的机制。
The adaptive response of Escherichia coli protects cells against the mutagenic and toxic effects of alkylating agents. This response is controlled by the Ada protein, which not only functions as the transcriptional activator of the ada and alkA genes but also possesses two DNA methyltransferae activities. Ada is converted into an efficient transcriptional activator by transferring a methyl group from a DNA methylphosphotriester to its own Cys-69 residue and then binds to a DNA sequence (the Ada box) present in both the ada and alkA promoters. Although the Ada protein initially appeared to regulate the ada and alkA genes in a similar fashion, our studies show that the wild-type Ada protein and its truncated derivatives can differentially regulate ada and alkA transcription. In vivo, lower levels of wild-type methylated Ada are needed to activate ada transcription than alkA transcription. In cells exposed to alkylating agents, the N-terminal half of Ada, which contains the DNA-binding domain, is sufficient for efficient activation of alkA, but not ada, transcription. Moreover, truncated derivatives containing 80-90% of Ada are extremely strong constitutive activators of ada but are only inducible activators of alkA transcription. These results suggest that the mechanism by which Ada activates ada transcription differs from that by which it activates alkA transcription.