Regulation of chromosome segregation in Escherichia coli.

Cell division is tightly coupled to DNA replication in Escherichia coli, as evidenced by the rarity of anucleate cells in steady state cultures. When DNA synthesis is arrested, cell division also comes to a halt and filamentous growth ensues, again with little formation of anucleate cells. To test the precise role of the SfiA division inhibitor during filamentous growth, we compared sfiA+ and sfiA- strains in their response to thymine starvation. More residual division was observed in the sfiA mutant culture, and autoradiographic analysis revealed that 13% of the final population consisted of cells of normal size containing no DNA compared to 0.9% in the thymine-starved sfiA+ culture. The SfiA division inhibitor is known to be synthesized massively during thymine starvation as part of the inducible SOS response. We conclude that it prevents aberrant division and formation of anucleate cells, thus assuring proper segregation when DNA synthesis is perturbed. The SfiC division inhibition mechanism, also associated with the SOS response, does not affect cell division during thymine starvation. On the other hand, an SOS-independent mechanism of division arrest clearly comes into play during thymine starvation of a sfiA sfiC mutant: although considerable aberrant division took place, the majority of the cells formed long filaments with 1 or 2 masses of DNA. Thus, E. coli assures proper chromosome segregation by two systems when DNA replication is perturbed: the rapid, efficient SfiA division inhibitor and a less stringent SOS-independent mechanism.