Adaptive response

Adaptive response

The adaptive response is a form of direct DNA repair in "E. coli" that is initiated against alkylation, particularly methylation, of guanine or thymine nucleotides or phosphate groups on the sugar-phosphate backbone of DNA. Under sustained exposure to low-level treatment with alkylating mutagens, "E. coli" can adapt to the presence of the mutagen, rendering subsequent treatment with high doses of the same agent less effective.Volkert MR. (1988). Adaptive response of Escherichia coli to alkylation damage. "Environ Mol Mutagen" 11(2):241-55.]

The adaptive response is mediated by the ada protein, which covalently transfers alkyl groups from the damaged DNA to one of its two cysteine residues, rendering the protein enzymatically dead. It is thus a "suicide" protein that reacts stoichiometrically rather than catalytically. Methylated ada acts as a transcription factor to initiate the adaptive response, promoting the expression of related genes such as alkA, alkB, aidB, and ada itself. The alkA gene product is a glycosylase, the aidB product is a flavin-containing protein,Rohankhedkar MS, Mulrooney SB, Wedemeyer WJ, Hausinger RP. (2006). The AidB component of the Escherichia coli adaptive response to alkylating agents is a flavin-containing, DNA-binding protein. "J Bacteriol" 188(1):223-30.] and alkB is an iron-dependent oxidoreductase;Yu B, Edstrom WC, Benach J, Hamuro Y, Weber PC, Gibney BR, Hunt JF. (2006). Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB. "Nature" 439(7078):879-84. ] all are involved in further DNA repairs of alkylation damage.


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