Adaptive response
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.[1] 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.[2] 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.[2] 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 [3] This process is irreversible.[2] and it can convert the protein from a weak to a strong activator of transcription,[4] increasing alkylating repair activity.[2]
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 cotrancribed from a single promoter. That said, they constitute an operon.[2] 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.[2]
- The ada gene has regulatory and repair activities, both really closed to each other. For the regulation happens, the ada protein must be activated, which is a consequence of the DNA repair activity [1]
- The alkA gene product is a glycosylase that can repairs a variety of lesions, removing a base from the sugar-phosphate backbone, producing an abasic site.[1]
- the aidB product is a flavin-containing protein,[5]
- alkB is an iron-dependent oxidoreductase;[6] and it's associated with DNA repair because this gene is able to repair lesions in phage DNA prior to infection. It's 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's 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;[1]
References
- ↑ 1.0 1.1 1.2 1.3 Landini, P, Volkert MR. (2000) Regulatory Responses of the Adaptive Response to Alkylation Damage: a Simple Regulon with Complex Regulatory Features J. Bacteriol 182(23): 6543–6549.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Volkert MR. (1988). Adaptive response of Escherichia coli to alkylation damage. Environ Mol Mutagen 11(2):241-55.
- ↑ Begley, T.; Samson, L. Mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism. Trends in Biochemical Sciences, v. 28, n. 1, p. 2-5, 2003.,
- ↑ Sedgwick, B., Robins, P., Totty, Nick., Lindahl, Tomas.Functional Domains and Methyl Acceptor Sites of the Escherichia coli Ada Protein*. v. 263. n 9. p 4430-4433, 1998.
- ↑ 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.
- ↑ 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.
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