Regulatory Responses of the Adaptive Response to Alkylation Damage: a Simple Regulon with Complex Regulatory Features

Alkylation damage to DNA occurs when cells encounter alkylating agents in the environment or when cellular metab-olism produces active alkylators. To cope with DNA alkylation, cells have evolved genes that encode proteins with alkylation-specific DNA repair activities. In Escherichia coli, the main response specific for alkylation damage has been called the adaptive response (53). The adaptive response genes are in-duced upon exposure to exogenous alkylators by Ada-depen-dent induction, and also during stationary phase by rpoS-de-pendent gene expression, possibly to prevent accumulation of DNA damage due to increased endogenous production of al-kylating agents. Recent studies of the regulatory mechanisms of Ada protein and the various responses of the individual promoters regulated by this protein has revealed a complexity of regulation not initially recognized. In this review we describe the roles of the Ada-regulated genes and the regulatory mech-anisms that activate gene expression from the three Ada-de-pendent promoters. We will focus on Ada-dependent induc-tion of the adaptive response genes, fine tuning of individual gene expression according to the growth phase, and the role played by Ada in shutting off the adaptive response.