Chromosome organization in bacteria: mechanistic insights into genome structure and function

Abstract

Bacterial chromosomes are folded to compact DNA and facilitate cellular processes. Studying model bacteria has revealed aspects of chromosome folding that are applicable to many species. Primarily controlled by nucleoid-associated proteins, chromosome folding is hierarchical, from large-scale macrodomains to smaller-scale structures that influence DNA transactions, including replication and transcription. Here we review the environmentally regulated, architectural and regulatory roles of nucleoid-associated proteins and the implications for bacterial cell biology. We also highlight similarities and differences in the chromosome folding mechanisms of bacteria and eukaryotes.

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Fig. 1: DNA is locally folded by nucleoid-associated proteins in bacteria, histones in eukaryotes and the evolutionarily conserved SMC complex.
Fig. 2: SMC proteins function as loop-extruding factors.
Fig. 3: Chromosomes are hierarchically organized in bacteria and eukaryotes.
Fig. 4: MukBEF moves along the chromosome as a ‘rock climber’.
Fig. 5: Environmental stimuli induce changes in chromosome organization.
Fig. 6: Modulation of transcription by nucleoid-associated proteins.
Fig. 7: Chromosome organization has an impact on chromosome segregation and cell cycle progression.

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Acknowledgements

The authors thank the Netherlands Organization for Scientific Research (VICI 016.160.613) (R.T.D.), the Wellcome Trust (212193/Z/18/Z) (D.C.G.), the Leverhulme Trust (RPG-2018–198) (D.C.G.), the UK Biotechnology and Biological Sciences Research Council (BB/H010289/1) (D.C.G.) and the Human Frontier Science Program (HFSP; RGP0014/2014) (R.T.D. and D.C.G.) for funding of current research in their laboratories.

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All authors researched data for the article, substantially contributed to discussion of the content and wrote the article. R.T.D. and D.C.G. reviewed and edited the manuscript before submission.

Correspondence to Remus T. Dame or David C. Grainger.

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Glossary

Chromosome

An essential molecule containing some or all of the genes required by an organism to survive and reproduce. Whereas chromosomes are made of DNA, not all DNA is chromosomal. Extrachromosomal DNA molecules such as plasmids also encode genes, although these genes are not absolutely required for an organism’s survival and reproduction.

Chromatin

A compact macromolecular complex of DNA and structuring proteins.

Nucleoids

Structures found in prokaryotic cells that contain chromosomes, bound proteins and other associated molecules (for example, RNAs). Nucleoids are functionally similar to the nuclei of eukaryotic cells but are not enclosed within a membrane. Nucleoids can be found in eukaryotic organelles believed to be bacterial in origin.

Genome

The complete set of genes encoded by the DNA content of a given organism. The genome includes genes encoded by chromosomal and extrachromosomal DNA, and intervening non-coding regions.

Nucleoid-associated proteins

(NAPs). A broad term to describe any proteins implicated in organizing bacterial chromosomes. Here we consider structural maintenance of chromosomes (SMC) proteins as NAPs due to their association with the nucleoid and their role in shaping nucleoid structure. SMC proteins — discovered later than other NAPs and initially studied primarily in the context of chromosome segregation — have historically (and in our view unjustly) not been classified as NAPs.

Nucleoprotein

A generic term, applicable to prokaryotes and eukaryotes, to describe DNA in complex with bound proteins.

Plectonemes

DNA loops in which the double-stranded DNA is wrapped around itself as a result of supercoiling.

Supercoiled

Pertains to supercoiling, which is underwinding or overwinding of the double helix that causes the double-stranded DNA to fold into higher-order structures: plectonemes and toroids. To alter DNA supercoiling levels, enzymatic breaking and rejoining of DNA strands is required.

Topoisomerase

An enzyme that alters DNA supercoiling by breaking and rejoining DNA strands. Mechanistically, topoisomerases are distinguished by whether they break and rejoin either a single strand (type I) or both strands (type II).

Replichores

The sections of a chromosome between the origin and the terminus of replication. Circular chromosomes are usually divided into a left replichore and a right replichore.

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Dame, R.T., Rashid, F.M. & Grainger, D.C. Chromosome organization in bacteria: mechanistic insights into genome structure and function. Nat Rev Genet (2019). https://doi.org/10.1038/s41576-019-0185-4

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