Mutants ofdnaAcosare inviable at 30°C because DnaAcos hyperinitiates, leading to new replication forks that apparently collide from behind with stalled forks, thereby generating lethal double-strand breaks. By comparison, an elevated level of DnaA also induces extra initiations, but lethality occurs only in strains defective in repairing double-strand breaks. To explore the model that the chromosomal level of DnaAcos, or the increased abundance of DnaA, increases initiation frequency by, escaping or overcoming pathways that control initiation, respectively, we developed a genetic selection and identifiedseqA,datA,dnaNandhda, which function in pathways that either act atoriCor modulate DnaA activity. To assess each pathway's relative effectiveness, we used genetically inactivated strains, and quantified initiation frequency after elevating the level of DnaA. The results indicate that thehda-dependent pathway has a stronger effect on initiation than pathways involvingseqAanddatA.Testing the model that DnaAcos overinitiates because it fails to respond to one or more regulatory mechanisms, we show thatdnaAcosis unresponsive tohdaanddnaN, which encodes the β clamp, and alsodatA, a locus proposed to titer excess DnaA. These results explain how DnaAcos hyperinitiates to interfere with viability.