Abstract

Bacterial cells growing in steady state maintain a 1:1:1 relationship between an appropriate mass increase, a round of DNA replication plus sister chromosome segregation, and cell division. This is accomplished without the cell cycle engine found in eukaryotic cells. We propose here a formal logic, and an accompanying mechanism, for how such coordination could be provided in E. coli. Completion of chromosomal and divisome-related events would lead, interactively, to a “progression control complex” (PCC) which provides integrated physical coupling between sister terminus regions and the nascent septum. When a cell has both (i) achieved a sufficient mass increase, and (ii) the PCC has developed, a conformational change in the PCC occurs. This change results in “progression permission,” which triggers both onset of cell division and release of terminus regions. Release of the terminus region, in turn, directly enables a next round of replication initiation via physical changes transmitted through the nucleoid. Division and initiation are then implemented, each at its own rate and timing, according to conditions present. Importantly: (i) the limiting step for progression permission may be either completion of the growth requirement or the chromosome/divisome processes required for assembly of the PCC; and, (ii) the outcome of the proposed process is granting of permission to progress, not determination of the absolute or relative timings of downstream events. This basic logic, and the accompanying mechanism, can explain coordination of events in both slow and fast growth conditions; can accommodate diverse variations and perturbations of cellular events; and is compatible with existing mathematical descriptions of the E. coli cell cycle. Also, while our proposition is specifically designed to provide 1:1:1 coordination among basic events on a “per-cell cycle” basis, it is a small step to further envision permission progression is also the target of basic growth rate control. In such a case, the rate of mass accumulation (or its equivalent) would determine the length of the interval between successive permission events and, thus, successive cell divisions and successive replication initiations.

Highlights

  • AND OVERVIEWAll cells growing in steady state must ensure a 1:1:1 relationship among doublings of cell mass, rounds of chromosome duplication/segregation and cell divisions

  • We suggest that the proposed process could serve for coordination, and as the mechanism by which occurrence of cell division [and an accompanying round of initiation(s)] is linked to cell growth conditions

  • It is less clear when and how the sensing of growth status occurs and this input may be independent of progression control complex” (PCC) development or feed directly into PCC development itself (Figure 1A legend). In any of these cases, progression permission would occur as soon as PCC development is complete. Once both the growth and chromosome/divisiome requirements have been met, the PCC would undergo a conformational change that concomitantly: (i) triggers onset of septum closure; and (ii) releases the terminus domain from divisome components

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Summary

AND OVERVIEW

All cells growing in steady state must ensure a 1:1:1 relationship among doublings of cell mass, rounds of chromosome duplication/segregation and cell divisions. Once both the growth and chromosome/divisiome requirements have been met, the PCC would undergo a conformational change that concomitantly: (i) triggers onset of septum closure (and cell division); and (ii) releases the terminus domain from divisome components (and thereby allowing a round of replication initiation to occur whenever other requirements and required components are present). Such a process would be an attractive way to achieve coordination (and control) in the absence of a eukaryotic-like cell cycle engine

FORMAL LOGIC
ACCOMMODATIONS AND
CELLULAR EVENTS WITH GROWTH
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