Biology subjects

Afanasyev, A. Y.

Publications and source records attributed to Afanasyev, A. Y..

3 recordsLinked to original sources

bioRxiv2023

Multi-plateau force-extension curves of long double-stranded DNA

When highly stretched, double-stranded DNA exhibits a plateau region in its force-extension curve. Using a bead-spring coarse-grained dynamic model based on a non-convex potential, we predict that a long double-stranded DNA fragment made of several consecutive segments with substantially different plateau force values for each segment will exhibit multiple distinct plateau regions in the force-extension curve under physiologically relevant solvent conditions. For example, a long composite double-stranded (ds) DNA fragment consisting of two equal-length segments characterized by two different plateau force values, such as the poly(dA-dT)-poly(dG-dC) fragment, is predicted to exhibit two distinct plateau regions in its force-extension curve; a long composite dsDNA fragment consisting of three segments having three different plateau force values is predicted to have three distinct plateau regions. The formation of mixed states of slightly and highly stretched DNA, co-existing with macroscopically distinct phases of uniformly stretched DNA is also predicted. When one of the segments overstretches, the extensions of the segments can differ drastically. For example, for the poly(dA-dT)-poly(dG-dC) composite fragment, in the middle of the first plateau, 96.7 % of the total extension of the fragment (relative to Lx/L0{approx} 1.0) comes from the poly(dA-dT) segment, while only 3.3 % of it comes from the poly(dG-dC) segment. The order of the segments has little effect on the force-extension curve or the distribution of conformational states. We speculate that the distinct structural states of stretched double-stranded DNA may have functional importance. For example, these states may modulate, in a sequence-dependent manner, the rate of double-stranded DNA processing by key cellular machines. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/532320v2_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@fc52forg.highwire.dtl.DTLVardef@15abedaorg.highwire.dtl.DTLVardef@a7fbbborg.highwire.dtl.DTLVardef@7fc8e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Stretching of long double-stranded DNA and RNA described by the same model.

We propose a bead-spring model that accurately reproduces a variety of experimental force-extension curves of long double-stranded DNA and RNA, including torsionally constrained and unconstrained DNA, and negatively supercoiled DNA. A key feature of the model is a specific non-convex energy function of the spring. We provide an algorithm for obtaining five required parameters of the model from experimental force-extension curves. In the plateau region of the force-extension curves, our molecular dynamics simulations show that the polymer separates into a mix of weakly and strongly stretched states without forming macroscopically distinct phases.

biophysics↗

bioRxiv2022

The probability of chromatin to be at the nuclear lamina has no systematic effect on its transcription level.

Multiple studies have demonstrated a negative correlation between gene expression and the positioning of genes at the nuclear envelope (NE) lined by nuclear lamina. In this paper, we ask whether there is a causal, systematic relationship between the expression level of the groups of genes in topologically associating domains (TADs) of Drosophila nuclei and the probabilities of TADs to be found at the NE. To investigate the nature of this possible relationship, we combine a coarse-grained dynamic model of the entire Drosophila nucleus with genome-wide gene expression data; we analyze the TAD averaged transcription levels of genes against the probabilities of individual TADs to be near the NE in the control and lamins-depleted nuclei. Our findings demonstrate that, within the statistical error margin, the stochastic positioning of Drosophila melanogaster TADs at the NE does not, by itself, systematically affects the mean level of gene expression in these TADs, while the expected negative correlation is confirmed. The correlation is weak and disappears completely for TADs not containing lamina-associated domains (LADs) or TADs containing LADs, considered separately. Verifiable hypotheses of the underlying mechanism for the presence of correlation without causality are discussed.

cell biology↗