Crosstalk Regulation Between Bacterial Chromosome Replication and Chromosome Partitioning

Abstract

Despite much effort, the bacterial cell cycle has proved difficult to study and understand. Bacteria do not conform to the standard eukaryotic model of sequential cell-cycle phases. Instead, for example, bacteria overlap their phases of chromosome replication and chromosome partitioning. In "eukaryotic terms," bacteria simultaneously perform "S-phase" and "mitosis" whose coordination is absolutely required for rapid growth and survival. In this review, we focus on the signaling "crosstalk," meaning the signaling mechanisms that advantageously commit bacteria to start both chromosome replication and chromosome partitioning. After briefly reviewing the molecular mechanisms of replication and partitioning, we highlight the crosstalk research from Bacillus subtilis, Vibrio cholerae, and Caulobacter crescentus. As the initiator of chromosome replication, DnaA also mediates crosstalk in each of these model bacteria but not always in the same way. We next focus on the C. crescentus cell cycle and describe how it is revealing novel crosstalk mechanisms. Recent experiments show that the novel nucleoid associated protein GapR has a special role(s) in starting and separating the replicating chromosomes, so that upon asymmetric cell division, the new chromosomes acquire different fates in C. crescentus's distinct replicating and non-replicating cell types. The C. crescentus PopZ protein forms a special cell-pole organizing matrix that anchors the chromosomes through their centromere-like DNA sequences near the origin of replication. We also describe how PopZ anchors and interacts with several key cell-cycle regulators, thereby providing an organized subcellular environment for more novel crosstalk mechanisms.

Keywords: DnaA; GapR; PopZ; cell cycle; chromosome replication; partitioning.

Figure 1

The C. crescentus cell cycle emphasizing asymmetric chromosome replication and partitioning. (A) The cell cycle conceptually starts on the left with the swarmer cell (Sw). It has one circular chromosome that is held at the flagellated cell pole by the centromere-like (parS) DNA linked to the origin of replication (Cori). The swarmer cell next differentiates into a non-motile and replicating stalked cell (St). Coincident with this cell differentiation, the chromosome replication and partitioning phases initiate apparently simultaneously, and they continue together for much of the cell cycle. The partitioning movement of parS-Cori has an initial slow phase that uses GapR protein and a later fast phase that requires the partitioning protein ParA (see text for further details). This slow partitioning phase overlaps the chromosome “symmetry breaking” step (*) of the cell cycle, which symmetrically channels the duplicated parS-Cori regions and eventually the entire chromosomes into distinct replicating (stalked cell) and non-replicating (swarmer cell) compartments. The blue cytoplasmic shading represents the activity (presence and phosphorylation) of the master cell-cycle regulator CtrA, which among many functions bind Cori to repress replication in swarmer cells. Asymmetric cell division (Div) proceeds with the return of CtrA activity and the building of a new polar flagellum. Eventually the two distinct cell types are formed. (B) A closer look at the cell poles during the above cell cycle. On the left, an early stalked cell pole where the parS-Cori region has been released from the PopZ matrix protein (not shown) and where rising DnaA activity first acts at parS DnaA boxes before acting at the Cori DnaA boxes. Although GapR binds broad regions of the chromosome, its strongest peaks are around the parS-Cori DNA. Next, a stalked cell pole immediately following the initiation of chromosome replication. One duplicated parS-Cori region reattaches to the old PopZ matrix at the stalked pole (symbolized by the broad arrow, the ParB bridge is not shown). The other duplicated parS-Cori region moves slowly away with the aid of GapR before its fast movement driven by ParA toward the other cell pole. On the right, both poles of a dividing cell. At the swarmer pole, the translocated parS-Cori region is attached to the new PopZ matrix that formed coincidentally with its arrival. At the opposite stalked pole, the parS-Cori region is released from PopZ roughly coincident with stalked cell reentry into another round of chromosome replication.