Allostery: DNA Does It, Too

Chaires, Jonathan B.

doi:10.1021/cb800070s

Cited by 34 publications

(42 citation statements)

References 20 publications

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“…A soft, correlated stretching motion in DNA remains the simplest consistent explanation of the experimental results and is compatible with independent observations of allosteric behavior in DNA [reviewed in (8)]. However, we agree with Becker and Everaers that radially amplified bending fluctuations should have been large enough to detect in the measured variance data.…”

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confidence: 92%

Response to Comment on “Remeasuring the Double Helix”

Mathew-Fenn

Das

Fenn

et al. 2009

Science

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We measured the mean and variance of end-to-end length in short DNA fragments in solution and reported evidence of DNA stretching that is cooperative over more than two turns of the double helix. Becker and Everaers suggest that the structural fluctuations we observed arise from bending motions of the DNA, rather than stretching. We present three experimental tests of this bendingbased explanation. W e recently reported on distance distributions between gold nanocrystals attached to the 3′-hydroxyl groups of short DNA duplexes (1, 2). Our data exhibit two unexpected features: The variance in end-to-end distance grows rapidly with duplex length, and the increase occurs in a nonlinear fashion. We interpret the results to be a manifestation of a soft, correlated stretching motion in DNA. Based on coarse-grained simulations of DNA structural fluctuations, Becker and Everaers (3) offer an alternative explanation: that the observed variances arise from bending motions of the DNA that are amplified through the linker attachments to the nanocrystal particles.As a qualitative interpretation of their simulation results, Becker and Everaers (3) suggest that the axial displacement of the nanocrystal centers from the ends of the DNA duplex acts like a lever arm to amplify bending fluctuations. In (1), we reported values for the bending-induced variance in end-to-end length computed according to the wormlike chain (WLC) model. When these values are increased by the axial amplification factor of Becker and Everaers [a factor of (l + axial 0 ) 2 /l 2 , where axial 0 is the axial offset of the nanocrystals from the duplex ends, fit to be~24 Å], they still only account for a fraction of the observed variance: 1% and 19% respectively for the 10-and 35-base-pair (bp) duplexes.The simulation results of Becker and Everaers (3) appear to be dominated by a different phenomenon: The radial offset of the nanocrystal centers from the helix axis acts as a lever arm to amplify the effect of duplex bending on the internanocrystal distance (Fig. 1A). In our experiments, the nanocrystals were attached to 3′-hydroxyl groups near the edge of the duplex cylinder (fit to be~9 Å off of the axis; D, radial offset).Depending on its direction, a bend in the duplex could either bring the two radially offset nanocrystals closer together or move them farther apart. Thus, the radial-offset phenomenon broadens distributions symmetrically, overcoming one of the objections to a bending-based explanation of our data. This radial-offset amplification is maximal when the two nanocrystals are positioned on the same side of the DNA cylinder and close to zero when the nanocrystals are positioned on opposite sides of the cylinder. Thus, the radially amplified bending model predicts a sinusoidal oscillation in variance with duplex length [proportional to D 2(1 + cosf); see Fig. 1A]. This oscillation matches the helix period of 10 bp, regardless of assumptions about the linkage between the nanocrystals and the DNA.To fit their model to our published variance da...

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supporting

confidence: 92%

Response to Comment on “Remeasuring the Double Helix”

Mathew-Fenn

Das

Fenn

et al. 2009

Science

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“…This fact is currently invoked in the recruitment of DNA-binding proteins and recognition of their binding sites. It is less acknowledged that this modulation also provides a strong basis for applying the concept of allostery to DNA [12]. As soon as DNA stiffness and structural cohesiveness extend beyond a single binding site, the strain induced by a first binding event generates a DNA deformation over a region embedding other binding sites, and possibly modifies their binding affinity.…”

Section: Protein-binding Event May Trigger Dna Allosteric Transitionsmentioning

confidence: 99%

“…Note that the focus in DNA allostery studies is often on thermodynamical coupling of binding events and associated cooperativity [12,45]. We also promote a mechanistic explanation in terms of a structural long-range coupling; the former is well-suited to fit experimental, e.g.…”

Section: Allosteric Transitions Occur In Mechanically Constrained Dnamentioning

confidence: 99%

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Chromatin fiber allostery and the epigenetic code

Lesne

Foray

Cathala

et al. 2015

J. Phys.: Condens. Matter

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Abstract. The notion of allostery introduced for proteins about fifty years ago has been extended since then to DNA allostery, where a locally triggered DNA structural transition remotely controls other DNA-binding events. We further extend this notion and propose that chromatin fiber allosteric transitions, induced by histone-tail covalent modifications, may play a key role in transcriptional regulation. We present an integrated scenario articulating allosteric mechanisms at different scales: allosteric transitions of the condensed chromatin fiber induced by histone-tail acetylation modify the mechanical constraints experienced by the embedded DNA, thus possibly controlling DNA-binding of allosteric transcription factors or further allosteric mechanisms at the linker DNA level. At a higher scale, different epigenetic constraints delineate different statistically dominant subsets of accessible chromatin fiber conformations, which each favors the assembly of dedicated regulatory complexes, as detailed on the emblematic example of the mouse Igf2-H19 gene locus and its parental imprinting. This physical view offers a mechanistic and spatially structured explanation of the observed correlation between transcriptional activity and histone modifications. The evolutionary origin of allosteric control supports to speak of an "epigenetic code", by which events involved in transcriptional regulation are encoded in histone modifications in a context-dependent way.

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“…Allostery has been deeply studied for proteins, where it has been characterized as one of the main mechanisms of control of their activities (5–7). Much less studied, but equally important, DNA-mediated allostery has been attributed a crucial role in the control of DNA–protein interactions (8–17). Most cases of cooperativity in DNA can be explained by a ‘direct read-out’ mechanism.…”

Section: Introductionmentioning

confidence: 99%

Allosterism and signal transfer in DNA

Balaceanu

Pérez

Dans

et al. 2018

Nucleic Acids Research

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We analysed the basic mechanisms of signal transmission in DNA and the origins of the allostery exhibited by systems such as the ternary complex BAMHI–DNA–GRDBD. We found that perturbation information generated by a primary protein binding event travels as a wave to distant regions of DNA following a hopping mechanism. However, such a structural perturbation is transient and does not lead to permanent changes in the DNA geometry and interaction properties at the secondary binding site. The BAMHI–DNA–GRDBD allosteric mechanism does not occur through any traditional models: direct (protein-protein), indirect (reorganization of the secondary site) readout or solvent-release. On the contrary, it is generated by a subtle and less common entropy-mediated mechanism, which might have an important role to explain other DNA-mediated cooperative effects.

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Allostery: DNA Does It, Too

Cited by 34 publications

References 20 publications

Response to Comment on “Remeasuring the Double Helix”

Response to Comment on “Remeasuring the Double Helix”

Chromatin fiber allostery and the epigenetic code

Allosterism and signal transfer in DNA

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