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Bacterial DNA segregation by the actin-like MreB protein

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Faithful chromosome segregation is vital to all organisms. Eukaryotic cells use the tubulin-based cytoskeleton to segregate their chromosomes during mitosis. A handful of papers have provided convincing evidence that, in bacteria, this task is accomplished by the actin homolog MreB. In particular, a recent study by Gitai et al. demonstrates that MreB specifically binds to and segregates the replication origin of the bacterial chromosome.

Introduction

An inherent feature in all living organisms is the faithful distribution of genetic material from the mother cell into daughter cell compartments. Defects in chromosome segregation produce cells that are aneuploid – a situation that can have dire consequences such as miscarriages in humans or cell death. Therefore, it is not surprising that cells have developed systems for ensuring high-fidelity DNA segregation. In eukaryotes, the process of DNA segregation is well understood. During the early stages of mitosis, replicated chromosomes condense to form paired sister-chromatid structures that align at the mid-cell. Subsequently, the mitotic spindle apparatus, which consists of microtubule fibres anchored via kinetochores to the centromeres pulls the sister chromatids towards opposite cell poles [1].

Unlike mitosis, the molecular mechanisms underlying DNA segregation in bacteria have remained obscure, and central issues, such as whether there is active versus passive movement of chromosomes or whether chromosome cohesion takes place, were, and still are, debated. Perhaps the most influential hypothesis for how chromosomes segregate in bacteria was proposed by Francois Jacob and coworkers [2] as part of their seminal replicon model, which suggests that the origins of the sister chromosomes are anchored to the cell membrane at a central position of the cell. Cell elongation and insertion of new cell membrane between the attachment sites of the two chromosomes would thus provide the motive force to segregate the chromosomes into the daughter cell compartments. In the replicon model, chromosome segregation is essentially a passive process, a view that was supported by the lack of any conspicuous intracellular cytoskeletal structures that could serve a mitotic-like function. However, numerous reports in which modern cytological techniques have been applied to study the subcellular localization of chromosomal regions, specifically the origin of replication (oriC), are now challenging the concept of passive DNA segregation. Studies in Bacillus subtilis, Escherichia coli and Caulobacter crescentus have established that, soon after replication, the two oriC copies are moved rapidly apart to sites near the cell poles and that this movement is independent of cell growth. These observations are consistent with the existence of active mechanisms, which provide the force and directionality required for the accurate segregation of chromosomal origin DNA 3, 4.

Section snippets

Could MreB form a bacterial mitotic-like machine?

It is now clear that bacteria contain true homologs of both tubulin (FtsZ) and actin (MreB and ParM). Could cytoskeletal elements contribute to DNA segregation in bacteria? Indeed, the DNA segregation machinery encoded by the E. coli plasmid R1 specifies a simple prokaryotic analog of the eukaryotic spindle apparatus. The plasmid-encoded ParM protein, an actin homolog, forms F-actin-like filaments that are responsible for the active movement of plasmid copies to opposite cell poles 5, 6. The

Inhibitor confirms role for MreB in chromosome segregation

Recent convincing evidence for a direct role of MreB in chromosome segregation in Caulobacter crescentus was presented by the Shapiro laboratory [19]. They used a small molecule, S-(3,4-dichlorobenzyl)isothiourea (A22), that was originally identified in a screen for compounds that induce anucleate E. coli cells and a change in cell morphology from the normal rod-shape to a spherical form [20]. When administered to Caulobacter cells, A22 mimics the effects of MreB depletion and causes a rapid

Concluding remarks

The observations described here reveal that, surprisingly, Nature has chosen to use actin and tubulin for reciprocal purposes in two different domains of life: in most eukaryotic cell types, actin is a fundamental component of the cytokinetic ring, whereas tubulin forms the mitotic spindle fibers. By contrast, in bacteria, the ubiquitous tubulin-like FtsZ protein forms the cytokinetic ring, whereas the actin-like proteins ParM and MreB form mitotic-like machineries that segregate DNA [4]. MreB

Acknowledgements

This work was supported by the Danish Biotechnology Instrument Center (DABIC) and the Carlsberg Foundation.

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