Unwrapping of DNA-protein complexes under external stretching

A DNA-protein complex modelled by a semiflexible chain and an attractive spherical core is studied in the situation when an external stretching force is acting on one end monomer of the chain while the other end monomer is kept fixed in space. Without stretching force, the chain is wrapped around the core. By applying an external stretching force, unwrapping of the complex is induced. We study the statics and the dynamics of the unwrapping process by computer simulation and simple phenomenological theory. We find two different scenarios depending on the chain stiffness: For a flexible chain, the extension of the complex scales linearly with the external force applied. The sphere-chain complex is disordered, i.e. there is no clear winding of the chain around the sphere. For a stiff chain, on the other hand, the complex structure is ordered, which is reminiscent to nucleosome. There is a clear winding number and the unwrapping process under external stretching is discontinuous with jumps of the distance-force curve. This is associated to discrete unwinding processes of the complex. Our predictions are of relevance for experiments, which measure force-extension curves of DNA-protein complexes, such as nucleosome, using optical tweezers.Comment: 8 pages, 7 figure

Axial turbulent flow in a circular pipe containing a fixed eccentric core

The turbulent flow of air through a circular pipe containing a fixed eccentric core was investigated at one air flow and one fixed eccentricity

How does torsional rigidity affect the wrapping transition of a semiflexible chain around a spherical core?

We investigated the effect of torsional rigidity of a semiflexible chain on the wrapping transition around a spherical core, as a model of nucleosome, the fundamental unit of chromatin. Through molecular dynamics simulation, we show that the torsional effect has a crucial effect on the chain wrapping around the core under the topological constraints. In particular, the torsional stress (i) induces the wrapping/unwrapping transition, and (ii) leads to a unique complex structure with an antagonistic wrapping direction which never appears without the topological constraints. We further examine the effect of the stretching stress for the nucleosome model, in relation to the unique characteristic effect of the torsional stress on the manner of wrapping

All-or-none switching of transcriptional activity on single DNA molecules caused by a discrete conformational transition

Recently, it has been confirmed that long duplex DNA molecules with sizes larger than several tens of kilo-base pairs (kbp), exhibit a discrete conformational transition from an elongated coil state to a compact globule state upon the addition of various kinds of chemical species that usually induce DNA condensation. In this study, we performed a single-molecule observation on a large DNA, Lambda ZAP II DNA (ca. 41 kbp), in a solution containing RNA polymerase and substrates along with spermine, a tetravalent cation, at different concentrations, by use of fluorescence staining of both DNA and RNA. We found that transcription, or RNA production, is completely inhibited in the compact state, but is actively performed in the unfolded coil state. Such an all-or-none effect on transcriptional activity induced by the discrete conformational transition of single DNA molecules is discussed in relation to the mechanism of the regulation of large-scale genetic activity.Comment: 14 pages, 2 figure

Orientational correlations in confined DNA

We study how the orientational correlations of DNA confined to nanochannels depend on the channel diameter D by means of Monte Carlo simulations and a mean-field theory. This theory describes DNA conformations in the experimentally relevant regime where the Flory-de Gennes theory does not apply. We show how local correlations determine the dependence of the end-to-end distance of the DNA molecule upon D. Tapered nanochannels provide the necessary resolution in D to study experimentally how the extension of confined DNA molecules depends upon D. Our experimental and theoretical results are in qualitative agreement.Comment: Revised version including supplemental material, 7 pages, 8 figure

The BRG1 transcriptional coregulator

The packaging of genomic DNA into chromatin, often viewed as an impediment to the transcription process, plays a fundamental role in the regulation of gene expression. Chromatin remodeling proteins have been shown to alter local chromatin structure and facilitate recruitment of essential factors required for transcription. Brahma-related gene-1 (BRG1), the central catalytic subunit of numerous chromatin-modifying enzymatic complexes, uses the energy derived from ATP-hydrolysis to disrupt the chromatin architecture of target promoters. In this review, we examine BRG1 as a major coregulator of transcription. BRG1 has been implicated in the activation and repression of gene expression through the modulation of chromatin in various tissues and physiological conditions. Outstanding examples are studies demonstrating that BRG1 is a necessary component for nuclear receptor-mediated transcriptional activation. The remodeling protein is also associated with transcriptional corepressor complexes which recruit remodeling activity to target promoters for gene silencing. Taken together, BRG1 appears to be a critical modulator of transcriptional regulation in cellular processes including transcriptional regulation, replication, DNA repair and recombination

Scottish Firefighters Occupational Cancer and Disease Mortality Rates: 2000-2020

Background Increased mortality from cancers and other diseases has been reported in USA, Canadian, and Nordic firefighters. However, UK firefighters are understudied. Aims To determine whether UK firefighters suffer increased mortality from cancers and other diseases when compared with the general population. Methods Mortality from cancer and other diseases in Scottish male firefighters between 2000 and 2020 was compared with the general Scottish male population and expressed as standardized mortality ratios (SMRs) (with 95% confidence intervals, CI). Results Significant overall excess cancer mortality was found for Scottish firefighters compared with the general population (SMR 1.61, CI 1.42-1.81). Scottish firefighters were nearly three times more likely to die of malignant neoplasms (unspecified sites) (SMR 2.71, CI 1.71-4.00). Excess cancer mortality was also found for several site-specific cancers, including prostate (SMR 3.80, CI 2.56-5.29), myeloid leukaemia (SMR 3.17, CI 1.44-5.58), oesophagus (SMR 2.42, CI 1.69-3.29) and urinary system (kidney and bladder) (SMR 1.94, CI 1.16-2.91). Mortality from neoplasms of unknown behaviour was over six times greater in Scottish firefighters (SMR 6.37, CI 2.29-12.49). Additionally, significantly higher mortality was found for: acute ischaemic heart diseases (SMR 5.27, CI 1.90-10.33), stroke (SMR 2.69, CI 1.46-4.28), interstitial pulmonary diseases (SMR 3.04, CI 1.45-5.22), renal failure (SMR 3.28, CI 1.18-6.44) and musculoskeletal system diseases (SMR 5.64, CI 1.06-13.83). Conclusions UK firefighters suffer significant excess mortality from cancer and other diseases when compared with the general population. Preventative health monitoring and presumptive legislation are urgently required to protect UK firefighters’ health

Equation of state for polymer liquid crystals: theory and experiment

The first part of this paper develops a theory for the free energy of lyotropic polymer nematic liquid crystals. We use a continuum model with macroscopic elastic moduli for a polymer nematic phase. By evaluating the partition function, considering only harmonic fluctuations, we derive an expression for the free energy of the system. We find that the configurational entropic part of the free energy enhances the effective repulsive interactions between the chains. This configurational contribution goes as the fourth root of the direct interactions. Enhancement originates from the coupling between bending fluctuations and the compressibility of the nematic array normal to the average director. In the second part of the paper we use osmotic stress to measure the equation of state for DNA liquid crystals in 0.1M to 1M NaCl solutions. These measurements cover 5 orders of magnitude in DNA osmotic pressure. At high osmotic pressures the equation of state, dominated by exponentially decaying hydration repulsion, is independent of the ionic strength. At lower pressures the equation of state is dominated by fluctuation enhanced electrostatic double layer repulsion. The measured equation of state for DNA fits well with our theory for all salt concentrations. We are able to extract the strength of the direct electrostatic double layer repulsion. This is a new and alternative way of measuring effective charge densities along semiflexible polyelectrolytes.Comment: text + 5 figures. Submitted to PR