Cooperative kinking at distant sites in mechanically stressed DNA

Lionberger, Troy A.; Demurtas, Davide; Witz, Guillaume; Dorier, Julien; Lillian, Todd D.; Meyhöfer, Edgar; Stasiak, Andrzej

doi:10.1093/nar/gkr666

Cited by 41 publications

(53 citation statements)

References 56 publications

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“…In other words, the ligands appear to recognize molecular shape rather than unique chemical features of the DNA base pairs. Here that shape is the stiff, naturally straight pathway of short, double-helical DNA, which also seems to direct the elongated, elliptical shapes of small, torsionally stressed DNA minicircles captured in cryo electron microscopic images (30). The many ways in which a protein like HU can effect cyclization point to the advantage of its nonspecificity on the enhancement of DNA ring closure compared with sequencespecific ligands that bind with similar affinity to a single site.…”

Section: Discussionmentioning

confidence: 99%

DNA topology confers sequence specificity to nonspecific architectural proteins

Juan

Czapla

Grosner

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Topological constraints placed on short fragments of DNA change the disorder found in chain molecules randomly decorated by nonspecific, architectural proteins into tightly organized 3D structures. The bacterial heat-unstable (HU) protein builds up, counter to expectations, in greater quantities and at particular sites along simulated DNA minicircles and loops. Moreover, the placement of HU along loops with the "wild-type" spacing found in the Escherichia coli lactose (lac) and galactose (gal ) operons precludes access to key recognition elements on DNA. The HU protein introduces a unique spatial pathway in the DNA upon closure. The many ways in which the protein induces nearly the same closed circular configuration point to the statistical advantage of its nonspecificity. The rotational settings imposed on DNA by the repressor proteins, by contrast, introduce sequential specificity in HU placement, with the nonspecific protein accumulating at particular loci on the constrained duplex. Thus, an architectural protein with no discernible DNA sequencerecognizing features becomes site-specific and potentially assumes a functional role upon loop formation. The locations of HU on the closed DNA reflect long-range mechanical correlations. The protein responds to DNA shape and deformability-the stiff, naturally straight double-helical structure-rather than to the unique features of the constituent base pairs. The structures of the simulated loops suggest that HU architecture, like nucleosomal architecture, which modulates the ability of regulatory proteins to recognize their binding sites in the context of chromatin, may influence repressoroperator interactions in the context of the bacterial nucleoid.NA behaves differently in a cellular milieu than in aqueous salt solution. Proteins attach to widely spaced sites along genomic sequences in vivo and force the intervening DNA into loops much shorter in length than those expected from the natural deformational properties of the double helix. For example, the control of gene expression in Escherichia coli entails the formation of short DNA loops, some ∼100 bp steps in length, that preclude access of RNA polymerase to the signals needed to transcribe the enzymes encoded within various operons (1, 2). DNA of the same length tends to be highly extended in vitro, with very low chances of closing spontaneously into a loop (3, 4).Aside from the proteins that hold specific sequences at the ends of short DNA loops in place, the cellular environment includes a number of other components that influence the properties of DNA loops. For example, the naturally abundant, nonspecific E. coli heat-unstable (HU) protein plays important roles both in cellular processing and in shaping the architecture of the bacterial nucleoid. The dimeric protein introduces large deformations in DNA-sharp bends, helical untwisting, and helical axis dislocation (5)-that are central to its activity. The binding of HU to an AT-rich sequence element stabilizes loops important for repression of the galactose (ga...

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Section: Discussionmentioning

confidence: 99%

DNA topology confers sequence specificity to nonspecific architectural proteins

Juan

Czapla

Grosner

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…The minicircle size and supercoiling can be precisely controlled, the partitioning between twist and writhe can be studied either with gel electrophoresis or by imaging with AFM (27) or cryo-EM (28) and the presence of single stranded regions can be detected enzymatically (22,29–31). However, since none of these experimental techniques are able to provide detailed structural information for the stressed DNA loops, we have used computer simulation to compare the denaturation of small circles for three different sequences, to visualize the resulting structural defects within the minicircles, and to make predictions of the positions of these defects within the circles that should be experimentally testable given modest improvements in the biochemical methods available.…”

Section: Introductionmentioning

confidence: 99%

Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation

et al. 2016

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It is well established that gene regulation can be achieved through activator and repressor proteins that bind to DNA and switch particular genes on or off, and that complex metabolic networks determine the levels of transcription of a given gene at a given time. Using three complementary computational techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are constrained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any requirement for external signalling factors. Our models combine atomistic molecular dynamics (MD) with coarse-grained simulations and statistical mechanical calculations to span three distinct spatial resolutions and timescale regimes. While they give a consensus view of the non-locality of sequence-dependent denaturation in highly bent and supercoiled DNA loops, each also reveals a unique aspect of long-range informational transfer that occurs as a result of restraining the DNA within the closed loop of the minicircles.

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“…Long plasmids can display many crossings such as supercoils and plectonemic structures [14]. For shorter plasmids the phenomenon of cooperative kinking at distant sites has been studied [15]. The simplest cases are planar plasmids with no self-crossings, i.e., the centerline of the DNA is topologically equivalent to a circle.…”

Section: Planar Plasmidsmentioning

confidence: 99%

Total positive curvature of circular DNA

Bohr

Olsen

2013

Phys. Rev. E

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The properties of double-stranded DNA and other chiral molecules depend on the local geometry, i.e., on curvature and torsion, yet the paths of closed chain molecules are globally restricted by topology. When both of these characteristics are to be incorporated in the description of circular chain molecules, e.g., plasmids, it is shown to have implications for the total positive curvature integral. For small circular micro-DNAs it follows as a consequence of Fenchel's inequality that there must exist a minimum length for the circular plasmids to be double stranded. It also follows that all circular micro-DNAs longer than the minimum length must be concave, a result that is consistent with typical atomic force microscopy images of plasmids. Predictions for the total positive curvature of circular micro-DNAs are given as a function of length, and comparisons with circular DNAs from the literature are presented.

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Cooperative kinking at distant sites in mechanically stressed DNA

Cited by 41 publications

References 56 publications

DNA topology confers sequence specificity to nonspecific architectural proteins

DNA topology confers sequence specificity to nonspecific architectural proteins

Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation

Total positive curvature of circular DNA

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