The adaptive response is a form of direct DNA repair in E. coli that protects DNA from damage by external agents or by errors during replication. It 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. This mechanism has four related genes, also known as “SOS genes”: ada, alkA, alkB, and aidB, each one working in specific residues, all regulated by Ada protein.
The adaptive response is mediated by the ada protein (a part of the Ada regulon), which covalently transfers alkyl groups from the damaged DNA to one of its two active methyl acceptor cysteine residues: Cys69 and Cys321. Ada protein can repair the damage by transferring methyl groups from O6-methylguanine or O4-methylthymine to Cys321 and also from methylphosphotriesters to Cys69 residue This process is irreversible. and it can convert the protein from a weak to a strong activator of transcription, increasing alkylating repair activity.
The four SOS genes
Four genes have been identified that contribute to the adaptive response against methylating agents: ada, alkA, alkB and aidB. ada and alkB are cotranscribed from a single promoter. That said, they constitute an operon. The SOS genes share a common regulatory mechanism and constitutes a general defense against DNA damage. Cells that have deficiency in one or more SOS genes tend to have a slower response, leading to a higher DNA damage through ultraviolet radiation and others agents.