The DnaA protein is the key DNA initiation protein in Escherichia coli. Using transcriptional and translational fusions, comparative S1 nuclease mapping and immunoblot analysis, the regulation of dnaA in relation to inducible responses to DNA damage was studied. We found that DNA damage caused by mitomycin C (MC) and methyl methanesulfonate (MMS) led to a significant induction of the dnaA gene. These results strongly suggest that in response to DNA damage which inhibits DNA replication, an increased initiation capacity is induced at oriC and that, in addition to the known auto-repression, a new regulatory mechanism may be involved in the control of dnaA gene expression. Furthermore, this mechanism might be indirectly related to the SOS regulon, because lexA and recA mutants, which block the induction of the SOS response, prevent dnaA induction by MMS and MC.