page_title: Ada regulon
section_title: Regulation of transcription
hierarchical_section_title: Ada regulon / Regulation of transcription
caption_attribution_description: English: This describes the transcriptional activation of the Ada Regulon
context_page_description: In DNA repair, the Ada regulon is a set of genes whose expression is essential to adaptive response, which is triggered in prokaryotic cells by exposure to sub-lethal doses of alkylating agents. This allows the cells to tolerate the effects of such agents, which are otherwise toxic and mutagenic.
  The Ada response includes the expression of four genes: ada, alkA, alkB, and aidB. The product of ada gene, the Ada protein, is an activator of transcription of all four genes. DNA bases damaged by alkylation are removed by distinct strategies.
context_section_description: The Ada response includes the expression of four genes: ada, alkA, alkB, and aidB. The product of the ada gene, the Ada protein is an activator of transcription of all four genes.
  Ada has two active methyl acceptor cysteine residues that are required for demethylation of DNA. Both sites can become methylated when Ada protein transfers the methyl group from the appropriate DNA lesions to itself. This reaction is irreversible and methylated Ada (me-Ada) can act as a transcriptional activator.
  The Ada protein activates the transcription of the Ada regulon in two different ways. In case of the ada-alkB operon, and the aidB promoter, the N-terminal domain (AdaNTD) is involved in DNA binding and interacts with the a unit of RNA polymerase, whereas and the methylated C-terminal domain (me-AdaCTD) interacts with the σ₇₀ subunit of RNA polymerase. Although these interactions are independent, both are necessary for transcription activation.
  For activation of alkA gene, the AdaNTD interacts with both, the α and σ subunits of RNA polymerase, and activates transcription. In contrast to the ada and aidB promoters, the unmethylated form of the Ada protein, as well as methylated form of the AdaNTD, is able to activate the transcription at alkA.
  Methylated Ada is able to activate transcription by σS as well as σ₇₀ at both the ada and aidB promoters. In contrast, not only does me-Ada fail to stimulate alkA transcription by σS, but it negatively affects σS dependent transcription.
  Intracellular concentrations of σS increase when the cells reach stationary phase; this in turn results in a me-Ada mediated decrease in the expression of AlkA. Therefore, an increase in expression of the adaptive response genes, in parallel with the expression of genes producing endogenous alkylators during the stationary phase, prevents alkylation damage to DNA and mutagenesis.
caption: Ada Regulatory network
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