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Review
. 2012 Aug;45(3):257-299.
doi: 10.1017/S0033583512000054. Epub 2012 Jul 31.

Bullied no more: when and how DNA shoves proteins around

Jonathan M Fogg #  1 , Graham L Randall #  2   3 , B Montgomery Pettitt  2   3 , De Witt L Sumners  4 , Sarah A Harris  5 , Lynn Zechiedrich  1   2
Affiliations
Review

Bullied no more: when and how DNA shoves proteins around

Jonathan M Fogg et al. Q Rev Biophys. 2012 Aug.

Abstract

The predominant protein-centric perspective in protein-DNA-binding studies assumes that the protein drives the interaction. Research focuses on protein structural motifs, electrostatic surfaces and contact potentials, while DNA is often ignored as a passive polymer to be manipulated. Recent studies of DNA topology, the supercoiling, knotting, and linking of the helices, have shown that DNA has the capability to be an active participant in its transactions. DNA topology-induced structural and geometric changes can drive, or at least strongly influence, the interactions between protein and DNA. Deformations of the B-form structure arise from both the considerable elastic energy arising from supercoiling and from the electrostatic energy. Here, we discuss how these energies are harnessed for topology-driven, sequence-specific deformations that can allow DNA to direct its own metabolism.

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Figures

Fig. 1
Fig. 1
Supercoiling and protein–DNA interactions. Top left: the bacteriophage 434 repressor (PDB ID: 3CRO.pdb) has an enhanced affinity for overwound DNA (Koudelka, 1998). Top right: Hin recombinase (PDB ID: 1HCR.pdb) will only bind to a site containing a CAG/CTG triplet when the DNA is supercoiled (Bae et al. 2006). Bottom left: the FIS protein (PDB ID: 3JRE.pdb) is both a transcription factor and a nucleoid-associated protein that constrains negative supercoils (Stella et al. 2010). Bottom right: MerR (PDB ID: 1R8E.pdb) is a bacterial repressor that on binding Hg (II) activates mercury resistance genes by untwisting the DNA-binding site (Ansari et al. 1992).
Fig. 2
Fig. 2
Representative structure from a MD simulation of a highly underwound 90 bp d(GC)90 minicircle (Harris et al. 2008). Denatured regions are clearly visible within the duplex. Image was generated using Chimera (Pettersen et al. 2004).
Fig. 3
Fig. 3
Representative structures from MD simulations of d(GC)n minicircles (Harris et al. 2008), showing a relaxed 90 bp DNA circle (left), an underwound and writhed 178 bp minicircle (top right) and an overwound and writhed 178 bp circle (bottom right). Images generated using QuteMol (Tarini et al. 2006).
Fig. 4
Fig. 4
Representative structure from an MD simulation of a highly underwound (σ=−0.135) DNA duplex (Randall et al. 2009). The helix partitions into regions of localized structural failure allowing the remainder of the helix to adopt relaxed B-DNA. This is related to the ion atmosphere (bottom). Counterion densities are contoured in dark blue showing the expected signatures in the grooves of the B-DNA region and the atypical response in the regions of structural failure.
Fig. 5
Fig. 5
Base pair step parameters as a function of σ. The filled circles show the average values of the parameters over the last 4 ns of simulations of DNA helices with fixed σ in a system that prohibits writhe (Randall et al. 2009). The horizontal dashed lines are the values of a relaxed helix with the same sequence, as predicted by analysis of PDB structures (Olson et al. 1998). The sloped dashed line shows what the average twist would be if uniformly distributed over the length of the DNA.
Fig. 6
Fig. 6
Representative structure from an MD simulation of a highly overwound (σ=0.391) DNA duplex (Randall et al. 2009). The very high torsional strain is relieved by the formation of a 5 bp region of P-DNA, allowing the remainder of the helix to relax back to B-DNA (bottom). Counterion densities are contoured in dark blue showing the expected signatures in the grooves of the B-DNA region. In the region of P-DNA, counterions are highly concentrated near the intertwined negatively charged backbones.
Fig. 7
Fig. 7
The structure of a P-DNA region as determined by MD simulations. The DNA structure shown in Fig. 6 was rendered as a cartoon view with periodic boundary conditions translated to the center of the cartoon view to facilitate visualization of the P-DNA. The path of the DNA backbone is rendered as a red ribbon, bases are in blue.
Fig. 8
Fig. 8
Structure of HaeIII methyltransferase bound to a flipped base of DNA (Reinisch et al. 1995; PDB ID: 1DCT.pdb). The DNA helix is rendered in spheres of blue except for the flipped out cytosine, which is rendered in green. The methyltransferase is rendered as a gold ribbon.
Fig. 9
Fig. 9
Poisson–Boltzmann predictions of the effect of DNA twist on counterion concentrations. According to the calculations, the charge density of the helix decreases with decreasing twist thereby reducing the counterion condensation. These calculations assumed an ionic strength of 150 mM. Lk is calculated assuming the helix is a fragment of a 339 bp minicircle.
Fig. 10
Fig. 10
Poisson–Boltzmann predictions of counterion concentrations in the vicinity of juxtaposed 12 bp helices (Randall et al. 2006). The DNA helices are rendered in gray and oriented so that the viewer is looking down the axis of the helix on the right. Isosurfaces of the counterion concentrations are colored red (2 M), orange (1 M), yellow (0.5 M), and green (0.25 M). High concentrations of counterions `neck' in the inter-helical region as demonstrated by the orange region between the two helices. Reprinted from Randall et al. (2006) with permission.
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References

    1. Aggarwal A, Rodgers DW, Drottar M, Ptashne M, Harrison SC. Recognition of a DNA operator by the repressor of phage 434: a view at high resolution. Science. 1988;242:899–907. - PubMed
    1. Ahmad S, Kono H, Araúzo-Bravo MJ, Sarai A. Readout: structure-based calculation of direct and indirect readout energies and specificities for protein–DNA recognition. Nucleic Acids Research. 2006;34:W124–W127. - PMC - PubMed
    1. Allemand J-F, Bensimon D, Lavery R, Croquette V. Stretched and overwound DNA forms a Pauling-like structure with exposed bases. Proceedings of the National Academy of Sciences of the United States of America. 1998;95:14152–14157. - PMC - PubMed
    1. Anderson P, Bauer W. Supercoiling in closed circular DNA: dependence upon ion type and concentration. Biochemistry. 1978;17:594–601. - PubMed
    1. Ansari AZ, Chael ML, O'Halloran TV. Allosteric underwinding of DNA is a critical step in positive control of transcription by Hg-Mer. Nature. 1992;355:87–89. - PubMed

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