3,106 research outputs found
Dynamics of a bubble formed in double stranded DNA
We study the fluctuational dynamics of a tagged base-pair in double stranded
DNA. We calculate the drift force which acts on the tagged base-pair using a
potential model that describes interactions at base pairs level and use it to
construct a Fokker-Planck equation.The calculated displacement autocorrelation
function is found to be in very good agreement with the experimental result of
Altan-Bonnet {\it et. al.} Phys. Rev. Lett. {\bf 90}, 138101 (2003) over the
entire time range of measurement. We calculate the most probable displacements
which predominately contribute to the autocorrelation function and the
half-time history of these displacements.Comment: 11 pages, 4 figures. submitted to Phys. Rev. Let
Denaturation transition of stretched DNA
We generalize the Poland-Scheraga model to consider DNA denaturation in the
presence of an external stretching force. We demonstrate the existence of a
force-induced DNA denaturation transition and obtain the temperature-force
phase diagram. The transition is determined by the loop exponent for which
we find the new value such that the transition is second order
with in . We show that a finite stretching force
destabilizes DNA, corresponding to a lower melting temperature , in
agreement with single-molecule DNA stretching experiments.Comment: 5 pages, 3 figure
Dynamical scaling of the DNA unzipping transition
We report studies of the equilibrium and the dynamics of a general set of
lattice models which capture the essence of the force-induced or mechanical DNA
unzipping transition. Besides yielding the whole equilibrium phase diagram in
the force vs temperature plane, which reveals the presence of an interesting
re-entrant unzipping transition for low T, these models enable us to
characterize the dynamics of the process starting from a non-equilibrium
initial condition. The thermal melting of the DNA strands displays a model
dependent time evolution. On the contrary, our results suggest that the
dynamical mechanism for the unzipping by force is very robust and the scaling
behaviour does not depend on the details of the description we adopt.Comment: 6 pages, 4 figures, A shorter version of this paper appeared in Phys.
Rev. Lett. 88, 028102 (2002
Increased Expression of Tissue Factor and Receptor for Advanced Glycation End Products in Peripheral Blood Mononuclear Cells of Patients With Type 2 Diabetes Mellitus with Vascular Complications
The aim of the study was to determine the correlation between
the expression of tissue factor (TF) and the receptor
for advanced glycation end products (RAGEs) and vascular
complications in patients with longstanding uncontrolled
type 2 diabetes (T2D). TF and RAGE mRNAs as well as
TF antigen and activity were investigated in 21 T2D patients
with and without vascular complications. mRNA expression
was assessed by reverse transcriptase–polymerase
chain reaction (RT-PCR) in nonstimulated and advanced
glycation end product (AGE) albumin–stimulated peripheral
blood mononuclear cells (PBMCs). TF antigen expression
was determined by enzyme-linked immunosorbent assay
(ELISA) and TF activity by a modified prothrombin
time assay. Basal RAGE mRNA expression was 0.2 ± 0.06
in patients with complications and 0.05 ± 0.06 patients without
complications (P = .004). Stimulation did not cause any
further increase in either group. TF mRNA was 0.58 ± 0.29
in patients with complications and 0.21 ± 0.18 in patients
without complications (P = .003). Stimulation resulted in
a nonsignificant increase in both groups. Basal TF activity
(U/106 PBMCs) was 18.4 ± 13.2 in patients with complications
and 6.96 ± 5.2 in patients without complications (P =
.003). It increased 3-fold in both groups after stimulation
(P = .001). TF antigen (pg/106 PBMCs) was 33.7 ± 28.6 in
patients with complications, 10.4 ± 7.8 in patients without complications (P = .02). Stimulation tripled TF antigen in
both groups of patients (P = .001). The RAGE/TF axis is
up-regulated inT2Dpatients with vascular complications as
compared to patients without complications. This suggests
a role for this axis in the pathogenesis of vascular complications
in T2D
Pulling a polymer out of a potential well and the mechanical unzipping of DNA
Motivated by the experiments on DNA under torsion, we consider the problem of
pulling a polymer out of a potential well by a force applied to one of its
ends. If the force is less than a critical value, then the process is activated
and has an activation energy proportinal to the length of the chain. Above this
critical value, the process is barrierless and will occur spontaneously. We use
the Rouse model for the description of the dynamics of the peeling out and
study the average behaviour of the chain, by replacing the random noise by its
mean. The resultant mean-field equation is a nonlinear diffusion equation and
hence rather difficult to analyze. We use physical arguments to convert this in
to a moving boundary value problem, which can then be solved exactly. The
result is that the time required to pull out a polymer of segments
scales like . For models other than the Rouse, we argue that Comment: 11 pages, 6 figures. To appear in PhysicalReview
Setting the stage for cohesion establishment by the replication fork
Comment on: Rudra S, et al. Cell Cycle 2012; 2114-2
Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites
The positions of nucleosomes in eukaryotic genomes determine which parts of
the DNA sequence are readily accessible for regulatory proteins and which are
not. Genome-wide maps of nucleosome positions have revealed a salient pattern
around transcription start sites, involving a nucleosome-free region (NFR)
flanked by a pronounced periodic pattern in the average nucleosome density.
While the periodic pattern clearly reflects well-positioned nucleosomes, the
positioning mechanism is less clear. A recent experimental study by Mavrich et
al. argued that the pattern observed in S. cerevisiae is qualitatively
consistent with a `barrier nucleosome model', in which the oscillatory pattern
is created by the statistical positioning mechanism of Kornberg and Stryer. On
the other hand, there is clear evidence for intrinsic sequence preferences of
nucleosomes, and it is unclear to what extent these sequence preferences affect
the observed pattern. To test the barrier nucleosome model, we quantitatively
analyze yeast nucleosome positioning data both up- and downstream from NFRs.
Our analysis is based on the Tonks model of statistical physics which
quantifies the interplay between the excluded-volume interaction of nucleosomes
and their positional entropy. We find that although the typical patterns on the
two sides of the NFR are different, they are both quantitatively described by
the same physical model, with the same parameters, but different boundary
conditions. The inferred boundary conditions suggest that the first nucleosome
downstream from the NFR (the +1 nucleosome) is typically directly positioned
while the first nucleosome upstream is statistically positioned via a
nucleosome-repelling DNA region. These boundary conditions, which can be
locally encoded into the genome sequence, significantly shape the statistical
distribution of nucleosomes over a range of up to ~1000 bp to each side.Comment: includes supporting materia
Master equation approach to DNA-breathing in heteropolymer DNA
After crossing an initial barrier to break the first base-pair (bp) in
double-stranded DNA, the disruption of further bps is characterized by free
energies between less than one to a few kT. This causes the opening of
intermittent single-stranded bubbles. Their unzipping and zipping dynamics can
be monitored by single molecule fluorescence or NMR methods. We here establish
a dynamic description of this DNA-breathing in a heteropolymer DNA in terms of
a master equation that governs the time evolution of the joint probability
distribution for the bubble size and position along the sequence. The transfer
coefficients are based on the Poland-Scheraga free energy model. We derive the
autocorrelation function for the bubble dynamics and the associated relaxation
time spectrum. In particular, we show how one can obtain the probability
densities of individual bubble lifetimes and of the waiting times between
successive bubble events from the master equation. A comparison to results of a
stochastic Gillespie simulation shows excellent agreement.Comment: 12 pages, 8 figure
Transcription factors TFIIF and TFIIS promote transcript elongation by RNA polymerase II by synergistic and independent mechanisms
Recent evidence suggests that transcript elongation by RNA polymerase II (RNAPII) is regulated by mechanical cues affecting the entry into, and exit from, transcriptionally inactive states, including pausing and arrest. We present a single-molecule optical-trapping study of the interactions of RNAPII with transcription elongation factors TFIIS and TFIIF, which affect these processes. By monitoring the response of elongation complexes containing RNAPII and combinations of TFIIF and TFIIS to controlled mechanical loads, we find that both transcription factors are independently capable of restoring arrested RNAPII to productive elongation. TFIIS, in addition to its established role in promoting transcript cleavage, is found to relieve arrest by a second, cleavage-independent mechanism. TFIIF synergistically enhances some, but not all, of the activities of TFIIS. These studies also uncovered unexpected insights into the mechanisms underlying transient pauses. The direct visualization of pauses at near-base-pair resolution, together with the load dependence of the pause-entry phase, suggests that two distinct mechanisms may be at play: backtracking under forces that hinder transcription and a backtrack-independent activity under assisting loads. The measured pause lifetime distributions are inconsistent with prevailing views of backtracking as a purely diffusive process, suggesting instead that the extent of backtracking may be modulated by mechanisms intrinsic to RNAPII. Pauses triggered by inosine triphosphate misincorporation led to backtracking, even under assisting loads, and their lifetimes were reduced by TFIIS, particularly when aided by TFIIF. Overall, these experiments provide additional insights into how obstacles to transcription may be overcome by the concerted actions of multiple accessory factors
Bubble coalescence in breathing DNA: Two vicious walkers in opposite potentials
We investigate the coalescence of two DNA-bubbles initially located at weak
segments and separated by a more stable barrier region in a designed construct
of double-stranded DNA. The characteristic time for bubble coalescence and the
corresponding distribution are derived, as well as the distribution of
coalescence positions along the barrier. Below the melting temperature, we find
a Kramers-type barrier crossing behaviour, while at high temperatures, the
bubble corners perform drift-diffusion towards coalescence. The results are
obtained by mapping the bubble dynamics on the problem of two vicious walkers
in opposite potentials.Comment: 7 pages, 4 figure
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