Protein-induced bending and DNA cyclization.

Kahn, Jason D.; Crothers, Donald M.

doi:10.1073/pnas.89.14.6343

Cited by 166 publications

(142 citation statements)

References 38 publications

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“…Such behavior might allow RNA polymerase I to work at full load, which is a characteristic of ribosomal gene transcription. (iii) The natural superhelical conformation of the DNA could also enhance the affinity of proteins for DNA binding and hence stimulate transcription (38,58,59). Consistent with this latter possibility is the case of the transcription factor xUBF, which binds the upstream element of the promoter.…”

Section: Discussionsupporting

confidence: 52%

Modeling of DNA local parameters predicts encrypted architectural motifs in Xenopus laevis ribosomal gene promoter

Roux-Rouquié

Marilley²

2000

Nucleic Acids Research

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We have modeled local DNA sequence parameters to search for DNA architectural motifs involved in transcription regulation and promotion within the Xenopus laevis ribosomal gene promoter and the intergenic spacer (IGS) sequences. The IGS was found to be shaped into distinct topological domains. First, intrinsic bends split the IGS into domains of common but different helical features. Local parameters at inter-domain junctions exhibit a high variability with respect to intrinsic curvature, bendability and thermal stability. Secondly, the repeated sequence blocks of the IGS exhibit righthanded supercoiled structures which could be related to their enhancer properties. Thirdly, the gene promoter presents both inherent curvature and minor groove narrowing which may be viewed as motifs of a structural code for protein recognition and binding. Such pre-existing deformations could simply be remodeled during the binding of the transcription complex. Alternatively, these deformations could pre-shape the promoter in such a way that further remodeling is facilitated. Mutations shown to abolish promoter curvature as well as intrinsic minor groove narrowing, in a variant which maintained full transcriptional activity, bring circumstantial evidence for structurally-preorganized motifs in relation to transcription regulation and promotion. Using well documented X.laevis rDNA regulatory sequences we showed that computer modeling may be of invaluable assistance in assessing encrypted architectural motifs. The evidence of these DNA topological motifs with respect to the concept of structural code is discussed.

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Section: Discussionsupporting

confidence: 52%

Modeling of DNA local parameters predicts encrypted architectural motifs in Xenopus laevis ribosomal gene promoter

Roux-Rouquié

Marilley²

2000

Nucleic Acids Research

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“…At 10 different time points, 16 l of the reaction mixture was removed and the ligation was halted by the addition of 8 l of the proteinase K mixture described in reference 15. By varying the amount of ligase added, these experiments were performed over times ranging between 4 and 21 h. Reaction mixtures were heated and then analyzed in a 6% native gel as described previously (15). Dried gels were analyzed by PhosphorImaging (Molecular Dynamics).…”

Section: Methodsmentioning

confidence: 99%

“…The cyclization kinetics assay was performed essentially as described by Kahn and Crothers (15). Ligation substrates were constructed with plasmids (31 and 37 pBluescript II KS 11T15F) (15,27) that were gifts of David Fisher. Each contained a Max protein binding site located 31 or 37 bp from a sequence of six regularly spaced poly(dA) tracts, which induces an intrinsic bend.…”

Section: Methodsmentioning

confidence: 99%

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The SKN-1 Amino-Terminal Arm Is a DNA Specificity Segment

Kophengnavong

Carroll

Blackwell

1999

Molecular and Cellular Biology

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The Caenorhabditis elegans SKN-1 protein binds DNA through a basic region like those of bZIP proteins and through a flexible amino-terminal arm segment similar to those with which numerous helix-turn-helix proteins bind to bases in the minor groove. A recent X-ray crystallographic structure suggests that the SKN-1 aminoterminal arm provides only nonspecific DNA binding. In this study, however, we demonstrate that this segment mediates recognition of an AT-rich element that is part of the preferred SKN-1 binding site and thereby significantly increases the sequence specificity with which SKN-1 binds DNA. Mutagenesis experiments show that multiple amino acid residues within the arm are involved in binding. These residues provide binding affinity through distinct but partially redundant interactions and enhance specificity by discriminating against alternate sites. The AT-rich element minor groove is important for binding of the arm, which appears to affect DNA conformation in this region. This conformational effect does not seem to involve DNA bending, however, because the arm does not appear to affect a modest DNA bend that is induced by SKN-1. The data illustrate an example of how a small, flexible protein segment can make an important contribution to DNA binding specificity through multiple interactions and mechanisms.

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“…Cyclization experiments involve short DNA strands whose ends meet, resulting in a loop-like configuration. The resulting closed curves are called DNA minicircles, and are excellent specimens for the study of DNA mechanics, as they yield a naturally stressed state in which intrinsic properties are amplified relative to extrinsic thermal fluctuations (Shore, Langowski, and Baldwin 1981;Shore and Baldwin 1983;Kahn and Crothers 1992). To link conformational variability to basepair sequence, one may probe minicircles with slightly differing base-pair sequences, for example, CAP minicircles and TATA minicircles (Amzallag et al 2006; see Section 2), whose base-pair composition coincides in all but a few basis steps.…”

Section: Molecular Biophysicsmentioning

confidence: 99%

Detecting and Localizing Differences in Functional Time Series Dynamics: A Case Study in Molecular Biophysics

Tavakoli

Panaretos

2016

Journal of the American Statistical Association

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Motivated by the problem of inferring the molecular dynamics of DNA in solution, and linking them with its base-pair composition, we consider the problem of comparing the dynamics of functional time series (FTS), and of localizing any inferred differences in frequency and along curvelength. The approach we take is one of Fourier analysis, where the complete second-order structure of the FTS is encoded by its spectral density operator, indexed by frequency and curvelength. The comparison is broken down to a hierarchy of stages: at a global level, we compare the spectral density operators of the two FTS, across frequencies and curvelength, based on a Hilbert-Schmidt criterion; then, we localize any differences to specific frequencies; and, finally, we further localize any differences along the length of the random curves, that is, in physical space. A hierarchical multiple testing approach guarantees control of the averaged false discovery rate over the selected frequencies. In this sense, we are able to attribute any differences to distinct dynamic (frequency) and spatial (curvelength) contributions. Our approach is presented and illustrated by means of a case study in molecular biophysics: how can one use molecular dynamics simulations of short strands of DNA to infer their temporal dynamics at the scaling limit, and probe whether these depend on the sequence encoded in these strands? Supplementary materials for this article are available online.

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Protein-induced bending and DNA cyclization.

Cited by 166 publications

References 38 publications

Modeling of DNA local parameters predicts encrypted architectural motifs in Xenopus laevis ribosomal gene promoter

Modeling of DNA local parameters predicts encrypted architectural motifs in Xenopus laevis ribosomal gene promoter

The SKN-1 Amino-Terminal Arm Is a DNA Specificity Segment

Detecting and Localizing Differences in Functional Time Series Dynamics: A Case Study in Molecular Biophysics

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