title: Ada response - a strategy for repair of alkylated DNA in bacteria.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Damian
authors.initials: D
authors.lastname: Mielecki
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Grzesiuk
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004926:Escherichia coli / Q000187:drug effects* / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D018085:Regulon; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C090096:AidB protein, E coli; D000477:Alkylating Agents; D029968:Escherichia coli Proteins; D014157:Transcription Factors; D006899:Mixed Function Oxygenases; C466427:AlkB protein, E coli; C045675:Ada protein, E coli; D019853:O(6)-Methylguanine-DNA Methyltransferase; D045647:DNA Glycosylases; C076131:DNA-3-methyladenine glycosidase II
keywords: ALKBH; Ada proteins; Ada response; DNA repair; alkylating agents