Replication initiator DnaA binds at the Caulobacter centromere and enables chromosome segregation

Significance DnaA is an essential and conserved bacterial protein that enables the initiation of DNA replication. Although it is commonly held that the onset of bacterial chromosome segregation depends on the initiation of DNA replication, we have found that in Caulobacter crescentus , chromosome segregation can be induced in a DnaA-dependent, yet replication-independent manner. The chromosome replication origin, containing essential DnaA binding motifs, resides 8 kb from the centromere parS region that also contains DnaA binding motifs. The centromere parS region bound to the ParB partition protein initiates movement across the cell followed by the origin region. Mutations in a centromere DnaA motif that alter DnaA–centromere interaction exhibit aberrant patterns of ParB/ parS translocation, implicating DnaA in the process of chromosome segregation. During cell division, multiple processes are highly coordinated to faithfully generate genetically equivalent daughter cells. In bacteria, the mechanisms that underlie the coordination of chromosome replication and segregation are poorly understood. Here, we report that the conserved replication initiator, DnaA, can mediate chromosome segregation independent of replication initiation. It does so by binding directly to the parS centromere region of the chromosome, and mutations that alter this interaction result in cells that display aberrant centromere translocation and cell division. We propose that DnaA serves to coordinate bacterial DNA replication with the onset of chromosome segregation.