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Dynamic localization of proteins and DNA during a bacterial cell cycle

Key Points

  • Cellular differentiation and asymmetric cell division is an integral part of the cell cycle in the bacterium Caulobacter crescentus.

  • The timing of differentiation and cell-cycle events are tightly controlled by the regulated synthesis, activity, stability and localization of many proteins.

  • The CtrA transcriptional regulator controls the execution of several cell-cycle and differentiation events.

  • Cell-cycle-specific degradation and phosphorylation control the activity of CtrA during the cell cycle.

  • Kinases that are involved in CtrA phosphorylation dynamically localize to specific intracellular sites, which indicates that spatial cues might have a role in regulating CtrA activation.

  • The timing of DNA replication and the organization of the chromosome within the cell are coordinated with cell-cycle progression. Specific regions of the chromosome rapidly and dynamically move to specific intracellular sites during DNA replication.

  • DNA replication itself and the organization and compaction of the newly replicated DNA contribute to chromosome segregation.

  • An integrated approach is being used to understand the control of cell-cycle progression through the coordination of gene transcription, protein availability, activation by phosphorylation and intracellular localization.

Abstract

A cellular differentiation programme that culminates in an asymmetric cell division is an integral part of the cell cycle in the bacterium Caulobacter crescentus. Recent work has uncovered mechanisms that ensure the execution of many events at different times during the cell cycle and at specific places in the cell. Surprisingly, in this one-micron bacterial cell, the dynamic spatial disposition of regulatory proteins, structural proteins and specific regions of the chromosome are important components of both cell-cycle progression and the generation of daughter cells with different cell fates.

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Figure 1: Caulobacter crescentus cell cycle.
Figure 2: Genetic network controlled by the CtrA response regulator.
Figure 3: Intracellular location patterns of different two-component regulatory proteins that function to control cell-cycle progression and differentiation.
Figure 4: Model of chromosome organization and replisome localization during the Caulobacter cell cycle.

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Acknowledgements

Portions of the work described here were supported by grants from the National Institutes of Health. R.B.J. was supported by fellowships from EMBO and the Carlsberg Foundation.

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Correspondence to Lucy Shapiro.

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DATABASES

Entrez

Caulobacter crescentus genome

 Swiss-Prot

CckA

ccrM

CtrA

DivJ

DivK

DivL

DnaA

FlbD

fliQ

FtsA

FtsQ

ftsZ

lacZ

MukB

ParA

ParB

PleC

smc

Glossary

FLAGELLUM

The cell motility apparatus in swimming bacteria.

PILI

Long, thin organelles that are present on the outer surface of some bacteria, and are formed by polymerization of the pilin protein.

ORIGIN OF DNA REPLICATION

The specific region in the chromosome in which initiation of DNA replication takes place.

SECRETION APPARATUS

The machinery that transports proteins through the cytoplasmic membrane and the cell wall.

HEMI-METHYLATED

One DNA strand is methylated, whereas the other is unmethylated.

DNA METHYLTRANSFERASE

An enzyme that transfers methyl-groups from S-adenosylmethionine to specific adenines or cytosines in DNA.

LON PROTEASE

A bacterial ATP-dependent protease.

PHOSPHORELAY PATHWAYS

Complex pathways in which phosphoryl groups are transferred through several signal-transduction proteins before reaching the target protein.

DNA POLYMERASE III

The enzyme that replicates the bulk of the chromosomal DNA in bacteria.

TOPOISOMERASES

Enzymes that change DNA supercoiling by inserting or removing superhelical twists.

HELICASES

Enzymes that separate the two DNA strands in a double helix, which results in the formation of regions of single-stranded DNA.

REPLISOME

A multi-protein complex that contains all the enzymes that are required for DNA replication.

SUPERCOILING

The under- or over-twisting of the DNA superhelix, which results in the DNA being drawn in on itself.

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Jensen, R., Wang, S. & Shapiro, L. Dynamic localization of proteins and DNA during a bacterial cell cycle. Nat Rev Mol Cell Biol 3, 167–176 (2002). https://doi.org/10.1038/nrm758

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