Ada response - a strategy for repair of alkylated DNA in bacteria

FEMS Microbiol Lett. 2014 Jun;355(1):1-11. doi: 10.1111/1574-6968.12462. Epub 2014 Jun 6.


Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N(3)-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N(1)-methyladenine (1meA) and N(3)-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O(6)-methylguanine (O(6) meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA.

Keywords: ALKBH; Ada proteins; Ada response; DNA repair; alkylating agents.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alkylating Agents / toxicity*
  • DNA Damage*
  • DNA Glycosylases / metabolism
  • DNA Repair*
  • Escherichia coli / drug effects*
  • Escherichia coli / physiology*
  • Escherichia coli Proteins / metabolism
  • Mixed Function Oxygenases / metabolism
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism
  • Regulon*
  • Stress, Physiological*
  • Transcription Factors / metabolism


  • AidB protein, E coli
  • Alkylating Agents
  • Escherichia coli Proteins
  • Transcription Factors
  • Mixed Function Oxygenases
  • AlkB protein, E coli
  • Ada protein, E coli
  • O(6)-Methylguanine-DNA Methyltransferase
  • DNA Glycosylases
  • DNA-3-methyladenine glycosidase II