Adaptive response of escherichia coli to alkylation damage

Abstract

Treatment of cells with low levels of alkylating agents for extended periods of time causes them to become resistant to the lethal and mutagenic effects of subsequent high-level challenge treatments with alkylating agents. This increased resistance has been called the adaptive response to alkylation damage and results from the induction of an alkylation-specific DNA repair response. The adaptive response is most efficiently induced by methylating agents and is most effective against the lethal and mutagenic effects of methylation damage to DNA. Four genes have been identified as components of this response, ada, alkA, alkB and aidB. The functions of two of these genes are known. AlkA protein functions as a glycosylase that repairs N3-meA, N3-meG, O2-meT, and O2-meC residues in DNA, and Ada protein functions as an alkyltransferase that removes alkyl groups from O6-meG, O4-meT residues as well as methylphosphotriesters. After it interacts with methylated DNA, Ada protein functions as a positive regulatory element that controls the expression of the adaptive response by stimulating the expression of the ada-alkB operon, and the alkA and aidB genes.

DNA Repair and Genome Maintenance in Bacillus subtilis

“…For a complete and comprehensive review of the E. coli Ada response, we direct readers to previously published reviews (128,376,430). The Ada response occurs in many Gramnegative bacteria as well as some Gram-positive bacteria, including but not limited to B. subtilis, Bacillus thuringiensis, M. tuberculosis, and Micrococcus luteus (340,341,463).…”

Adaptive Response and Oxidative Stress

“…The involvement of DNA repair enzymes has since been confirmed. Those identified include adaA and adaB methyltransferases, both isolated from Bacillus subtilis ada mutants deficient in the adaptive response to alkylating agents (10); and AlkA, a repair glycosylase that repairs methylated DNA bases (11).…”

Induction of the alkA gene of Escherichia coli in gram-negative bacteria

“…Several DNA repair systems in bacteria have been described (12), the adaptive response to alkylating agents being one of the most clearly characterized (17,34,41). The main feature of this repair response is that treatment of cells with low levels of methylating and ethylating agents renders the cells more resistant to the mutagenic and toxic effects of much larger doses of these alkylating agents (13,29).…”