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ada

Domain

Consists of two domains. The 20 kDa N-terminal domain repairs the Sp diastereomer of methylphosphotriesters and, in its methylated form, binds DNA in a sequence-specific manner. The 19 kDa C-terminal domain repairs the mutagenic lesions O6-methylguanine. Each domain retains its activity when separated form the other.

Function

Involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. Repairs O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme (Cys-321). Also specifically repairs the Sp diastereomer of DNA methylphosphotriester lesions by the same mechanism, although the methyl transfer occurs onto a different cysteine residue (Cys-38). Cannot demethylate the other diastereomer, Rp-methylphosphotriester. This is a suicide reaction: the enzyme is irreversibly inactivated.

The methylation of Ada by methylphosphotriesters in DNA leads to its activation as a transcriptional regulator that activates the transcription of its own gene, ada, and other alkylation resistance genes, alkA, alkB and aidB.

Sequence Similarities

In the C-terminal section; belongs to the MGMT family.

Alternative names

b2213, JW2201, ada, Bifunctional transcriptional activator/DNA repair enzyme Ada, Regulatory protein of adaptive response

swissprot:P06134