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.

Highlights

  • BACTERIAL CELL CYCLES REQUIRE CROSSTALK AND COORDINATION. To ensure their survival and proliferation, bacteria overlap and compress cell-cycle processes that are complex and time consuming. This overlap in bacteria contrasts with eukaryotes, which have sequential and non-overlapping phases for chromosome replication (S-phase), partition/segregation, and cell-division/cytokinesis

  • Since fluorescently labeled ParB is bound to parS during this early slow-movement phase, how does parS-ParB move without ParA?. How do these early partitioning steps faithfully split chromosome symmetry to channel them toward two different cell fates (Figure 1A)? What are the regulators and the motors during the early partitioning steps? How do they communicate with chromosome replication? These questions are starting to be addressed in the following paragraphs

  • Somehow the parS-crescentus origin of replication (Cori) region is released from PopZ, and upon replication initiation, the duplicated DNA regions are separated such that one region seems to reattach, while the other moves slowly toward the quarter cell-length position

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Summary

INTRODUCTION

To ensure their survival and proliferation, bacteria overlap and compress cell-cycle processes that are complex and time consuming. ParA (Soj) can either delay or advance the start of oriC replication depending on its monomer versus dimer states and its contacts with ParB (Spo0J) Exactly how these factors link oriC/DnaA regulation to chromosome movements and perhaps to other cell-cycle processes remains vague and speculative. Chrom II seems to have an interesting parallel regulation with that of the Caulobacter crescentus (Ccr) chromosome, which will be described further below: As with most parABS systems, the Vc parS centromere locus in rctA binds Vc ParB2 and the Ccr parS binds Cr ParB Very interestingly, both centromere loci bind their main replication initiator proteins, Vc RctB (Gerding et al, 2015) and Ccr DnaA, respectively (Mera et al, 2014). How do these early partitioning steps faithfully split chromosome symmetry to channel them toward two different cell fates (Figure 1A)? What are the regulators and the motors during the early partitioning steps? How do they communicate with chromosome replication? These questions are starting to be addressed in the following paragraphs

B GapR parS Cori
CRESCENTUS DNAA ALSO SIGNALS CHROMOSOME PARTITIONING
CRESCENTUS PROTEIN POPZ IS A POLAR ORGANIZING “HUB”
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