Alkylating agents, which are widespread in the environment, also occur endogenously as primary and secondary metabolites. Such compounds have intrinsically extremely cytotoxic and frequently mutagenic effects, to which organisms have developed resistance by evolving multiple repair mechanisms to protect cellular DNA. One such defense against alkylation lesions is an inducible Adaptive (Ada) response. In Escherichia coli, the Ada response enhances cell resistance by the biosynthesis of four proteins: Ada, AlkA, AlkB, and AidB. The glycosidic bonds of the most cytotoxic lesion, N3-methyladenine (3meA), together with N3-methylguanine (3meG), O(2)-methylthymine (O(2)-meT), and O(2)-methylcytosine (O(2)-meC), are cleaved by AlkA DNA glycosylase. Lesions such as N1-methyladenine (1meA) and N3-methylcytosine (3meC) are removed from DNA and RNA by AlkB dioxygenase. Cytotoxic and mutagenic O(6)-methylguanine (O(6)meG) is repaired by Ada DNA methyltransferase, which transfers the methyl group onto its own cysteine residue from the methylated oxygen. We review (i) the individual Ada proteins Ada, AlkA, AlkB, AidB, and COG3826, with emphasis on the ubiquitous and versatile AlkB and its prokaryotic and eukaryotic homologs; (ii) the organization of the Ada regulon in several bacterial species; (iii) the mechanisms underlying activation of Ada transcription. In vivo and in silico analysis of various microorganisms shows the widespread existence and versatile organization of Ada regulon genes, including not only ada, alkA, alkB, and aidB but also COG3826, alkD, and other genes whose roles in repair of alkylated DNA remain to be elucidated. This review explores the comparative organization of Ada response and protein functions among bacterial species beyond the classical E. coli model.

中文翻译：

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微生物中烷基化DNA的诱导修复。

在环境中广泛存在的烷基化剂也作为主要和次要代谢产物以内源性形式存在。这类化合物具有内在的极强的细胞毒性和诱变作用，有机体通过进化多种修复机制来保护细胞DNA而产生了抗药性。一种针对烷基化损伤的防御措施是可诱导的适应性（Ada）反应。在大肠杆菌中，Ada响应通过四种蛋白（Ada，AlkA，AlkB和AidB）的生物合成增强细胞抗性。N3-甲基腺嘌呤（3meA）和N3-甲基鸟嘌呤（3meG），O（2）-甲基胸腺嘧啶（O（2）-meT）和O（2）-甲基胞嘧啶（O（ 2）-meC）被AlkA DNA糖基化酶切割。通过AlkB双加氧酶从DNA和RNA中去除了N1-甲基腺嘌呤（1meA）和N3-甲基胞嘧啶（3meC）等病变。具有细胞毒性和诱变性的O（6）-甲基鸟嘌呤（O（6）meG）由Ada DNA甲基转移酶修复，该酶将甲基从甲基化的氧转移到其自身的半胱氨酸残基上。我们审查（i）单个Ada蛋白Ada，AlkA，AlkB，AidB和COG3826，重点研究普遍存在且用途广泛的AlkB及其原核和真核同源物；（ii）Ada regulon在几种细菌中的组织；（iii）Ada转录激活的潜在机制。对各种微生物的体内和计算机分析表明，Ada regulon基因广泛存在并具有多种组织，不仅包括ada，alkA，alkB和aidB，还包括COG3826，alkD，在修复烷基化DNA中的作用的其他基因还有待阐明。这篇综述探讨了经典大肠杆菌模型以外细菌物种之间的Ada反应和蛋白质功能的比较组织。