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Adaptive response

The adaptive response to methylation damage is a bacterial DNA damage response pathway induced specifically upon exposure to DNA methylation damage. It is initiated independently of the SOS response. Bacteria such as Escherichia coli exposed to sub-lethal doses of methylation damage activate the Ada response pathway. This enables their survival to subsequent exposure to high doses of the same agent. The Ada response was first identified in E. coli; however, over the years diverse and widespread Ada response pathways have been identified across bacteria. The pathways typically vary in the domain organization of the regulatory protein that orchestrates the Ada response.

The E. coli Ada response
This response was first identified in E. coli. The E. coli adaptive response constitutes four genes: ada, alkA, alkB, and aidB, each one working in specific residues, all regulated by the E. coli Ada protein. The E. coli adaptive response is mediated by the Ada protein, which covalently transfers methylation damage from DNA to one of its two active methyl acceptor cysteine residues: Cys38 and Cys321. The Ada protein can repair damage by transferring methyl groups from O6-methylguanine or O4-methylthymine to Cys321 and also from methylphosphotriesters to Cys38 residue through an irreversible process. increasing alkylation repair activity. alkA The alkA gene product is a glycosylase that can repair a variety of lesions, removing a base from the sugar-phosphate backbone, producing an abasic site. alkB alkB is an iron-dependent oxidoreductase, and it is associated with DNA repair because this gene is able to repair lesions in phage DNA prior to infection. It has been also demonstrated that alkB is required for reactivation of MMS-treated (methylating agent methyl methanesulfonate) single-stranded phage and since there are no lesions to be removed, it has been suggested that alkBB is involved in replication of damaged template DNA. Also, the fact that alkB can confer resistance to a methylating agent it suggests that it functions by itself. == Mechanism ==
Mechanism
Although little is known about the mechanism of the adaptive response, it is believed that changes in gene transcription and the activation of cellular defenses are involved. It has recently been suggested that specific mechanistic pathways of the adaptive response can activate the important tumor suppressor protein p53. A key experiment that reveals the underlying mechanisms is that which involves the treatment with protein synthesis inhibitors to Oedogonium Chlamydomonas and Closterium cells. This experiment resulted in DNA-binding proteins being synthesized in the cells conditioned with the stressor. Furthermore, reverse adaptive response suggests that a high conditioning dose followed by a second low dose produces roughly the same magnitude of response. This could suggest that the mechanisms work by cellular response modulation, not prevention, to the impending damage. The adaptive response is not instantaneous and takes several hours to develop, however after development it can last for months given that the stressor exposure is limited and will not overwhelm the cell. This is known as being dose and time-dependent with a maximum response occurring at 4 hours after an initial conditioning dose of 100 cGy (centigray) radiation stressor. == References ==
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