DNA cruciform arms nucleate through a correlated but non-synchronous cooperative mechanism

Inverted repeat (IR) sequences in DNA can form non-canonical cruciform structures to relieve torsional stress. We use Monte Carlo simulations of a recently developed coarse-grained model of DNA to demonstrate that the nucleation of a cruciform can proceed through a cooperative mechanism. Firstly, a twist-induced denaturation bubble must diffuse so that its midpoint is near the centre of symmetry of the IR sequence. Secondly, bubble fluctuations must be large enough to allow one of the arms to form a small number of hairpin bonds. Once the first arm is partially formed, the second arm can rapidly grow to a similar size. Because bubbles can twist back on themselves, they need considerably fewer bases to resolve torsional stress than the final cruciform state does. The initially stabilised cruciform therefore continues to grow, which typically proceeds synchronously, reminiscent of the S-type mechanism of cruciform formation. By using umbrella sampling techniques we calculate, for different temperatures and superhelical densities, the free energy as a function of the number of bonds in each cruciform along the correlated but non-synchronous nucleation pathways we observed in direct simulations.Comment: 12 pages main paper + 11 pages supplementary dat

DNA word analysis based on the distribution of the distances between symmetric words

We address the problem of discovering pairs of symmetric genomic words (i.e., words and the corresponding reversed complements) occurring at distances that are overrepresented. For this purpose, we developed new procedures to identify symmetric word pairs with uncommon empirical distance distribution and with clusters of overrepresented short distances. We speculate that patterns of overrepresentation of short distances between symmetric word pairs may allow the occurrence of non-standard DNA conformations, such as hairpin/cruciform structures. We focused on the human genome, and analysed both the complete genome as well as a version with known repetitive sequences masked out. We reported several well-defined features in the distributions of distances, which can be classified into three different profiles, showing enrichment in distinct distance ranges. We analysed in greater detail certain pairs of symmetric words of length seven, found by our procedure, characterised by the surprising fact that they occur at single distances more frequently than expecte

Effects of DNA supercoiling on chromatin architecture

Disruptions in chromatin structure are necessary for the regulation of eukaryotic genomes, from remodelling of nucleosomes at the base pair level through to large-scale chromatin domains that are hundreds of kilobases in size. RNA polymerase is a powerful motor which, prevented from turning with the tight helical pitch of the DNA, generates over-wound DNA ahead of itself and under-wound DNA behind. Mounting evidence supports a central role for transcription-dependent DNA supercoiling in disrupting chromatin structure at all scales. This supercoiling changes the properties of the DNA helix in a manner that substantially alters the binding specificity of DNA binding proteins and complexes, including nucleosomes, polymerases, topoisomerases and transcription factors. For example, transient over-wound DNA destabilises nucleosome core particles ahead of a transcribing polymerase, whereas under-wound DNA facilitates pre-initiation complex formation, transcription factor binding and nucleosome core particle association behind the transcribing polymerase. Importantly, DNA supercoiling can also dissipate through DNA, even in a chromatinised context, to influence both local elements and large chromatin domains. We propose a model in which changes in unconstrained DNA supercoiling influences higher levels of chromatin organisation through the additive effects of DNA supercoiling on both DNA-protein and DNA-nucleosome interactions. This model links small-scale changes in DNA and chromatin to the higher-order fibre and large-scale chromatin structures, providing a mechanism relating gene regulation to chromatin architecture in vivo

Rain impact on FSO link attenuation based on theory and measurement

The FSO link becomes a usual mean of modern wireless communications. But it suffers from atmospheric particles causing attenuation. That´s why this random attenuation must be carefully considered by the FSO link design. As it is known the most serious atmospheric phenomenon is fog, and low cloudiness. But the rain attenuation (night mare of mm wave links) is not negligible on optical links, too. In this contribution we focus on rain attenuation from theoretical as well as experimental point of view. Statistics and rain event analysis are shown. There is an overview and a comparison of several formulas for rain attenuation derived from DSD or rain rate. Rain is not the worst phenomena for the transmission but we can’t neglect its influence on FSO. Only full understanding of influence of real atmosphere can lead to solution of a high availability of FSO systems

Soft Tissue Esthetics in Implant Dentistry

Dental implants have been considered to be a successful treatment modality. Recently, achieving a good osseointegration is not the ultimate goal for the restorative dentist. Successful implant treatment demands the best gingival esthetic success along with stability and function of the implant. This study was performed to obtain answers to some controversial points pertaining to esthetics and function of implants in maxilla. Immediate flapless implantation into the extraction sockets in maxillary anterior zone is an emerging treatment option in dentistry- the esthetic success of which was in debate for long. The proposed study compared the esthetic success of immediate flapless implants (ILA), to immediate implants with the need for flap (ILB) and, delayed implants (DSL) in single tooth restorations, in the anterior region of the maxilla. The other aim of the study was to find out if any relation exists between the interproximal crestal bone height and papilla height. Analysis was done irrespective of treatment procedure in the same study group using periodontal sounding and radiographs to find out the relation. From the study involving 106 participants, including 21 ILA, 22 ILB and 63 DSL cases, we received highest papillary index score of 2.6 average from group ILA, followed by ILB and DSL, after 3 months of prosthetic loading. From the periodontal sounding and radiographic study it was evident that, when the distance between the base of the contact point of crowns and height of interproximal bone was less than 5, the papilla was present 100 % of the time, but when the distance increased to 6 and more than 7 mm, the papilla was present only 46.5 and 24 percentage of the time respectively

Identification of Distinct Amino Acid Composition of Human Cruciform Binding Proteins

Cruciform structures are preferential targets for many architectural and regulatory proteins, as well as a number of DNA binding proteins with weak sequence specificity. Some of these proteins are also capable of inducing the formation of cruciform structures upon DNA binding. In this paper we analyzed the amino acid composition of eighteen cruciform binding proteins of Homo sapiens. Comparison with general amino acid frequencies in all human proteins revealed unique differences, with notable enrichment for lysine and serine and/or depletion for alanine, glycine, glutamine, arginine, tyrosine and tryptophan residues. Based on bootstrap resampling and fuzzy cluster analysis, multiple molecular mechanisms of interaction with cruciform DNA structures could be suggested, including those involved in DNA repair, transcription and chromatin regulation. The proteins DEK, HMGB1 and TOP1 in particular formed a very distinctive group. Nonetheless, a strong interaction network connecting nearly all the cruciform binding proteins studied was demonstrated. Data reported here will be very useful for future prediction of new cruciform binding proteins or even construction of predictive tool/web-based application

Identification of Distinct Amino Acid Composition of Human Cruciform Binding Proteins

Abstract: Cruciform structures are preferential targets for many architectural and regulatory proteins, as well as a number of DNA binding proteins with weak sequence specificity. Some of these proteins are also capable of inducing the formation of cruciform structures upon DNA binding. In this paper we analyzed the amino acid composition of eighteen cruciform binding proteins of Homo sapiens. Comparison with general amino acid frequencies in all human proteins revealed unique differences, with notable enrichment for lysine and serine and/or depletion for alanine, glycine, glutamine, arginine, tyrosine and tryptophan residues. Based on bootstrap resampling and fuzzy cluster analysis, multiple molecular mechanisms of interaction with cruciform DNA structures could be suggested, including those involved in DNA repair, transcription and chromatin regulation. The proteins DEK, HMGB1 and TOP1 in particular formed a very distinctive group. Nonetheless, a strong interaction network connecting nearly all the cruciform binding proteins studied was demonstrated. Data reported here will be very useful for future prediction of new cruciform binding proteins or even construction of predictive tool/web-based application