Pathways of mutagenesis and repair in Escherichia coli exposed to low levels of simple alkylating agents

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Abstract
Mutagenesis by simple alkylating agents is thought to occur by either a lexA+-dependent process called error-prone repair or a lex-independent process often attributed to mispairing during replication. Error-prone repair is responsible for the majority of mutants formed after a large dose of alkylating agent, but it is unlikely that it contributes significantly to mutagenesis during exposure to low concentrations of these chemicals. The mutagenicity of these low doses of alkylating agent is reduced by a repair system constitutively present in lexA+ cells but absent in lexA mutants. This system reduces mutagenesis until a 2nd error-free system, called the adaptive response, can be induced. The adaptive response is capable of dealing with a much larger amount of alkylation damage than the constitutive system and, when induced, appears to be able to reduce mutagenesis by both decreasing the number of sites available for mutagenesis and delaying the induction of error-prone repair enzymes. A model of chemically induced mutagenesis based on these findings is discussed which maintains that the observed mutation frequency is dependent on a race between these 2 error-free systems and the 2 mutagenic pathways.