The RepA protein of plasmid pSC101 controls Escherichia coli cell divisionthrough the SOS response

Although plasmid copy number varies widely among different plasmid species, normally copy number is maintained within a narrow range for any given pla smid. Such copy number control has been shown to occur by regulation of the rate of plasmid DNA replication. Here we report a novel mechanism by which the pSC101 plasmid also can detect an imbalance between the cellular level of its replication protein, RepA, and plasmid-borne RepA binding sites to inhibit bacterial DNA replication and delay host cell division when RepA is in relative excess. We show that delayed cell division occurs by RepA-medi ated induction of the SOS response and can be reversed by overexpression of the host DNA primase, DnaG. The effects of RepA excess are prevented by in troducing a surfeit of RepA binding sites. The mechanism reported here may help to limit variation in plasmid copy number and allow repopulation of ce lls with plasmids when copy number falls - potentially pre-empting plasmid loss in cultures of dividing cells.