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.^[1]

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,^[1] the aidB product is a flavin-containing protein,^[2] and alkB is an iron-dependent oxidoreductase;^[3] all are involved in further DNA repairs of alkylation damage.