Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nonlinear mechanical model constructed in a previous paper [Nuovo Cimento D 20, 833 (1998)] is developed in order to study the dynamics of the DNA double helix. It is assumed that the hydrophobic interaction between subsequent base pairs may be influenced by a RNA polymerase. The Lagrangian, constructed on the basis of "geometrical" properties of the DNA molecule, depends on time and contains first and second derivatives of the twist angle. The energy dissipation term is added to the dynamical equations resulting from the Lagrange formalism. It is proved that the system has pulse-like solitary wave solutions for which the dissipated energy is balanced by the energy pumped by the advancing RNA polymerase. The physical interpretation of our solution is the local untwisting of the DNA molecule during transcription of messenger RNA.
...
PMID:Chemically driven traveling waves in DNA. 1197 Jun 69

By monitoring the end-to-end extension of a mechanically stretched, supercoiled, single DNA molecule, we have been able directly to observe the change in extension associated with unwinding of approximately one turn of promoter DNA by RNA polymerase (RNAP). By performing parallel experiments with negatively and positively supercoiled DNA, we have been able to deconvolute the change in extension caused by RNAP-dependent DNA unwinding (with approximately 1-bp resolution) and the change in extension caused by RNAP-dependent DNA compaction (with approximately 5-nm resolution). We have used this approach to quantify the extent of unwinding and compaction, the kinetics of unwinding and compaction, and effects of supercoiling, sequence, ppGpp, and nucleotides. We also have used this approach to detect promoter clearance and promoter recycling by successive RNAP molecules. We find that the rate of formation and the stability of the unwound complex depend profoundly on supercoiling and that supercoiling exerts its effects mechanically (through torque), and not structurally (through the number and position of supercoils). The approach should permit analysis of other nucleic-acid-processing factors that cause changes in DNA twist and/or DNA compaction.
...
PMID:Promoter unwinding and promoter clearance by RNA polymerase: detection by single-molecule DNA nanomanipulation. 1503 53

The torque generated by RNA polymerase as it tracks along double-stranded DNA can potentially induce long-range structural deformations integral to mechanisms of biological significance in both prokaryotes and eukaryotes. In this paper, we introduce a dynamic computer model for investigating this phenomenon. Duplex DNA is represented as a chain of hydrodynamic beads interacting through potentials of linearly elastic stretching, bending, and twisting, as well as excluded volume. The chain, linear when relaxed, is looped to form two open but topologically constrained subdomains. This permits the dynamic introduction of torsional stress via a centrally applied torque. We simulate by Brownian dynamics the 100 micros response of a 477-base pair B-DNA template to the localized torque generated by the prokaryotic transcription ensemble. Following a sharp rise at early times, the distributed twist assumes a nearly constant value in both subdomains, and a succession of supercoiling deformations occurs as superhelical stress is increasingly partitioned to writhe. The magnitude of writhe surpasses that of twist before also leveling off when the structure reaches mechanical equilibrium with the torsional load. Superhelicity is simultaneously right handed in one subdomain and left handed in the other, as predicted by the "transcription-induced twin-supercoiled-domain" model [L. F. Liu and J. C. Wang, Proc. Natl. Acad. Sci. U.S.A. 84, 7024 (1987)]. The properties of the chain at the onset of writhing agree well with predictions from theory, and the generated stress is ample for driving secondary structural transitions in physiological DNA.
...
PMID:Transcription-driven twin supercoiling of a DNA loop: a Brownian dynamics study. 1548 74

Histone octamers show a heat-induced mobility along DNA. Recent theoretical studies have established two mechanisms that are qualitatively and quantitatively compatible with in vitro experiments on nucleosome sliding: octamer repositioning through one-base-pair twist defects and through ten-base-pair bulge defects. A recent experiment demonstrated that the repositioning is strongly suppressed in the presence of minor-groove binding DNA ligands. In the present study, we give a quantitative theory for nucleosome repositioning in the presence of such ligands. We show that the experimentally observed octamer mobilities are consistent with the picture of bound ligands blocking the passage of twist defects through the nucleosome. This strongly supports the model of twist defects inducing a corkscrew motion of the nucleosome as the underlying mechanism of nucleosome sliding. We provide a theoretical estimate of the nucleosomal mobility without adjustable parameters, as a function of ligand concentration, binding affinity, binding site orientation, temperature and DNA anisotropy. Having this mobility in hand, we speculate on the interaction between a nucleosome and a transcribing RNA polymerase, and suggest a novel mechanism that might account for polymerase-induced nucleosome repositioning on short DNA templates.
...
PMID:Theory of nucleosome corkscrew sliding in the presence of synthetic DNA ligands. 1550 1

DNA supercoiling is a major regulator of transcription in bacteria. Negative supercoiling acts both by promoting the formation of nucleoprotein structures containing wrapped DNA and by altering the twist of DNA. The latter affects the initiation of transcription by RNA polymerase as well as recombination processes. Here, we argue that although bacteria and eukaryotes differ in their mode of packaging DNA supercoils, increases in DNA twist are associated with chromatin folding and transcriptional silencing in both. Conversely, decreases in DNA twist are associated with chromatin unfolding and the acquisition of transcriptional competence. In other words, at the most fundamental level, the principles of genetic regulation are common to all organisms. The apparent differences in the details of regulation probably represent alternative methods of fine-tuning similar underlying processes.
...
PMID:A common topology for bacterial and eukaryotic transcription initiation? 1726 6

T7 RNA polymerase undergoes dramatic structural rearrangements in the transition from initiation to elongation. Two models have been proposed for promoter-bound intermediates late in the transition. (i) A subset of promoter interactions are maintained through completion of the protein conformational (twist) change, and (ii) concerted movement (shift) of all promoter-binding elements away from the growing DNA-RNA hybrid leads to an open intermediate, with large-scale domain rotations deferred until after promoter release. Fluorescence resonance energy transfer measurements provide very strong support for the latter.
...
PMID:Twisted or shifted? Fluorescence measurements of late intermediates in transcription initiation by T7 RNA polymerase. 1747 44

Eukaryotic mRNA transcription by RNA polymerase II is a highly regulated complex reaction involving numerous proteins. In order to control tissue and promoter specific gene expression, transcription factors must work in concert with each other and with the promoter DNA to form the proper architecture to activate the gene of interest. The TATA binding protein (TBP) binds to TATA boxes in core promoters and bends the TATA DNA. We have used quantitative solution fluorescence resonance energy transfer (FRET) and gel-based FRET (gelFRET) to determine the effect of TFIIA on the conformation of the DNA in TBP/TATA complexes and on the kinetic stability of these complexes. Our results indicate that human TFIIA decreases the angle to which human TBP bends consensus TATA DNA from 104 degrees to 80 degrees when calculated using a two-kink model. The kinetic stability of TBP/TATA complexes was greatly reduced by increasing the KCl concentration from 50 mM to 140 mM, which is more physiologically relevant. TFIIA significantly enhanced the kinetic stability of TBP/TATA complexes, thereby attenuating the effect of higher salt concentrations. We also found that TBP bent non-consensus TATA DNA to a lesser degree than consensus TATA DNA and complexes between TBP and a non-consensus TATA box were kinetically unstable even at 50 mM KCl. Interestingly, TFIIA increased the calculated bend angle and kinetic stability of complexes on a non-consensus TATA box, making them similar to those on a consensus TATA box. Our data show that TFIIA induces a conformational change within the TBP/TATA complex that enhances its stability under both in vitro and physiological salt conditions. Furthermore, we present a refined model for the effect that TFIIA has on DNA conformation that takes into account potential changes in bend angle as well as twist angle.
...
PMID:TFIIA changes the conformation of the DNA in TBP/TATA complexes and increases their kinetic stability. 1768 38

The empirical harmonic potential function of elastic network models (ENMs) is augmented by three- and four-body interactions as well as by a parameter-free connection rule. In the new bend-twist-stretch (BTS) model the complexity of the parametrization is shifted from the spatial level of detail to the potential function, enabling an arbitrary coarse graining of the network. Compared to distance cutoff-based Hookean springs, the approach yields a more stable parametrization of coarse-grained ENMs for biomolecular dynamics. Traditional ENMs give rise to unbounded zero-frequency vibrations when (pseudo)atoms are connected to fewer than three neighbors. A large cutoff is therefore chosen in an ENM (about twice the average nearest-neighbor distance), resulting in many false-positive connections that reduce the spatial detail that can be resolved. More importantly, the required three-neighbor connectedness also limits the coarse graining, i.e., the network must be dense, even in the case of low-resolution structures that exhibit few spatial features. The new BTS model achieves such coarse graining by extending the ENM potential to include three-and four-atom interactions (bending and twisting, respectively) in addition to the traditional two-atom stretching. Thus, the BTS model enables reliable modeling of any three-dimensional graph irrespective of the atom connectedness. The additional potential terms were parametrized using continuum elastic theory of elastic rods, and the distance cutoff was replaced by a competitive Hebb connection rule, setting all free parameters in the model. We validate the approach on a carbon-alpha representation of adenylate kinase and illustrate its use with electron microscopy maps of E. coli RNA polymerase, E. coli ribosome, and eukaryotic chaperonin containing T-complex polypeptide 1, which were difficult to model with traditional ENMs. For adenylate kinase, we find excellent reproduction (>90% overlap) of the ENM modes and B factors when BTS is applied to the carbon-alpha representation as well as to coarser descriptions. For the volumetric maps, coarse BTS yields similar motions (70%-90% overlap) to those obtained from significantly denser representations with ENM. Our Python-based algorithms of ENM and BTS implementations are freely available.
...
PMID:Bend-twist-stretch model for coarse elastic network simulation of biomolecular motion. 1970 37

From supercoiled DNA to the tight loops of DNA formed by some gene repressors, DNA in cells is often highly bent. Despite evidence that transcription by RNA polymerase (RNAP) is affected in systems where DNA is deformed significantly, the mechanistic details underlying the relationship between polymerase function and mechanically stressed DNA remain unclear. Seeking to gain additional insight into the regulatory consequences of highly bent DNA, we hypothesize that tightly looping DNA is alone sufficient to repress transcription. To test this hypothesis, we have developed an assay to quantify transcription elongation by bacteriophage T7 RNAP on small, circular DNA templates approximately 100 bp in size. From these highly bent transcription templates, we observe that the elongation velocity and processivity can be repressed by at least two orders of magnitude. Further, we show that minicircle templates sustaining variable levels of twist yield only moderate differences in repression efficiency. We therefore conclude that the bending mechanics within the minicircle templates dominate the observed repression. Our results support a model in which RNAP function is highly dependent on the bending mechanics of DNA and are suggestive of a direct, regulatory role played by the template itself in regulatory systems where DNA is known to be highly bent.
...
PMID:Bending the rules of transcriptional repression: tightly looped DNA directly represses T7 RNA polymerase. 2071 97

In humans, a germline mutation (c.309C>G) in the TWIST1 oncogene may predispose to breast cancer and its expression has been associated with tumour progression and metastasis. In this study, the feline TWIST1 gene was screened for sequence variations in 37 neoplastic and eight hyperplastic mammary gland lesions from cats. In addition, mRNA levels were examined in 15 mammary tumours and three cases of mammary hyperplasia by quantitative real-time reverse-transcriptase PCR. Feline mammary carcinomas had significantly lower levels of expression of TWIST1 mRNA than benign mammary tumours. No variations were identified in the TWIST1 coding region in feline mammary tumours and the mutation described in humans was not detected. However, two germline variants in the TWIST1 gene intron were identified in four and three carcinomas, respectively: GQ167299:g.535delG and GQ167299:g.460C>T. There was no association between these sequence alterations and TWIST1 mRNA levels.
...
PMID:Sequence variation and mRNA expression of the TWIST1 gene in cats with mammary hyperplasia and neoplasia. 2133 Jan 72


<< Previous 1 2 3 Next >>

---