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Review
. 2012 Jul;1819(7):632-8.
doi: 10.1016/j.bbagrm.2011.12.007. Epub 2012 Jan 3.

The importance of being supercoiled: how DNA mechanics regulate dynamic processes

Affiliations
Review

The importance of being supercoiled: how DNA mechanics regulate dynamic processes

Laura Baranello et al. Biochim Biophys Acta. 2012 Jul.

Abstract

Through dynamic changes in structure resulting from DNA-protein interactions and constraints given by the structural features of the double helix, chromatin accommodates and regulates different DNA-dependent processes. All DNA transactions (such as transcription, DNA replication and chromosomal segregation) are necessarily linked to strong changes in the topological state of the double helix known as torsional stress or supercoiling. As virtually all DNA transactions are in turn affected by the torsional state of DNA, these changes have the potential to serve as regulatory signals detected by protein partners. This two-way relationship indicates that DNA dynamics may contribute to the regulation of many events occurring during cell life. In this review we will focus on the role of DNA supercoiling in the cellular processes, with particular emphasis on transcription. Besides giving an overview on the multiplicity of factors involved in the generation and dissipation of DNA torsional stress, we will discuss recent studies which give new insight into the way cells use DNA dynamics to perform functions otherwise not achievable. This article is part of a Special Issue entitled: Chromatin in time and space.

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Figures

Figure 1
Figure 1. Basics of DNA topology and its relevance to DNA transaction
The DNA topology is described quantitatively by the twist of double helix and by the number of times the helix crosses over on itself (plectoneme). Plectonemic structures are typically formed by bacterial plasmids. B) A graphical illustration showing the generation of supercoiling during transcription and replication. If polymerases are moving without rotation, then due to its helical structure, the DNA must be screwed through the protein complexes. In this case, the templates rotate around its axis as indicated by curved arrows.
Figure 2
Figure 2. Strategies to assess the DNA topology inside of the cells
A) Psoralen intercalates preferentially into undertwisted DNA and, upon exposure to UV-light, crosslinks its strands. DNA supercoiling in vivo can be monitored through the extent of photo-crosslinking between different loci in the cell. B) Dynamic torsional stress propagating from an activated promoter between the loxP sites is trapped in the DNA circle excised by Cre-recombinase. Two-dimensional electrophoresis of the circles gives an accurate accounting of DNA supercoiling generated during transcription.
Figure 3
Figure 3. Long range regulatory events due to transcription-generated DNA supercoiling
A) Torsional stress modulates the conformation of chromatin, promoting unwrapping of DNA from the histones ahead of RNA polymerase (RNAP) and rewrapping behind it. B) During transcription of c-myc gene the melting of the supercoil-sensitive sequence FUSE promotes the recruitment of factors that enhance (FBP) or repress (FIR) the transcription. C) According to the level of torsional stress, the CT-element located upstream of the c-myc promoter can flip between different conformations (double-stranded, single-stranded and G-quadruplex/ i-motif) which dictate the binding of specific transcription factors. D) The chromatin remodeling in the promoter of CSF1 favors the formation of Z-DNA which stabilizes the open chromatin structure. (-) means negative supercoils, (+) means positive supercoils. E) Single-stranded structures in supercoiled region provide the flexibility needed to juxtapose distal elements.

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References

    1. Dulbecco R, Vogt M. Evidence for a Ring Structure of Polyoma Virus DNA. Proc Natl Acad Sci U S A. 1963;50:236–243. - PMC - PubMed
    1. Wang JC. Interaction between DNA and an Escherichia coli protein omega. J Mol Biol. 1971;55:523–533. - PubMed
    1. Vologodskii AV, Levene SD, Klenin KV, Frank-Kamenetskii M, Cozzarelli NR. Conformational and thermodynamic properties of supercoiled DNA. J Mol Biol. 1992;227:1224–1243. - PubMed
    1. Vologodskii AV, Cozzarelli NR. Conformational and thermodynamic properties of supercoiled DNA. Annu Rev Biophys Biomol Struct. 1994;23:609–643. - PubMed
    1. Hatfield GW, Benham CJ. DNA topology-mediated control of global gene expression in Escherichia coli. Annu Rev Genet. 2002;36:175–203. - PubMed