Recombination-independent homologous pairing represents a prominent yet largely enigmatic feature of chromosome biology. As suggested by studies in the fungus Neurospora crassa, this process may be based on the direct pairing of homologous DNA molecules. Theoretical search for the DNA structures consistent with those genetic results has led to an all-atom model in which the B-DNA conformation of the paired double helices is strongly shifted toward C-DNA.
View Article and Find Full Text PDFRepeat-induced point mutation is a genetic process that creates cytosine-to-thymine (C-to-T) transitions in duplicated genomic sequences in fungi. Repeat-induced point mutation detects duplications (irrespective of their origin, specific sequence, coding capacity, and genomic positions) by a recombination-independent mechanism that likely matches intact DNA double helices directly, without relying on the annealing of complementary single strands. In the fungus Neurospora crassa, closely positioned repeats can induce mutation of the adjoining nonrepetitive regions.
View Article and Find Full Text PDFThe pairing of homologous chromosomes represents a critical step of meiosis in nearly all sexually reproducing species. In many organisms, pairing involves chromosomes that remain apparently intact. The mechanistic nature of homology recognition at the basis of such pairing is unknown.
View Article and Find Full Text PDFThe ability of homologous chromosomes (or selected chromosomal loci) to pair specifically in the apparent absence of DNA breakage and recombination represents a prominent feature of eukaryotic biology. The mechanism of homology recognition at the basis of such recombination-independent pairing has remained elusive. A number of studies have supported the idea that sequence homology can be sensed between intact DNA double helices in vivo.
View Article and Find Full Text PDFIn some fungi, a premeiotic process known as repeat-induced point mutation (RIP) can accurately identify and mutate nearly all gene-sized DNA repeats present in the haploid germline nuclei. Studies in Neurospora crassa have suggested that RIP detects sequence homology directly between intact DNA double helices, without strand separation and without the participation of RecA-like proteins. Those studies used the aggregated number of RIP mutations as a simple quantitative measure of RIP activity.
View Article and Find Full Text PDFAnomalous nonexponential relaxation in hydrated biomolecules is commonly attributed to the complexity of the free-energy landscapes, similarly to polymers and glasses. It was found recently that the hydrogen-bond breathing of terminal DNA base pairs exhibits a slow power-law relaxation attributable to weak Hamiltonian chaos, with parameters similar to experimental data. Here, the relationship is studied between this motion and spectroscopic signals measured in DNA with a small molecular photoprobe inserted into the base-pair stack.
View Article and Find Full Text PDFMolecular recognition between two double stranded (ds) DNA with homologous sequences may not seem compatible with the B-DNA structure because the sequence information is hidden when it is used for joining the two strands. Nevertheless, it has to be invoked to account for various biological data. Using quantum chemistry, molecular mechanics, and hints from recent genetics experiments, I show here that direct recognition between homologous dsDNA is possible through the formation of short quadruplexes due to direct complementary hydrogen bonding of major-groove surfaces in parallel alignment.
View Article and Find Full Text PDFThe statistics of Poincaré recurrences is studied for the base-pair breathing dynamics of an all-atom DNA molecule in a realistic aqueous environment with thousands of degrees of freedom. It is found that at least over five decades in time the decay of recurrences is described by an algebraic law with the Poincaré exponent close to β=1.2.
View Article and Find Full Text PDFNucleic Acids Res
December 2014
The apparently anomalous flexibility of DNA on short length scales has attracted a lot of attention in recent years. We use atomic force microscopy (AFM) in solution to directly study the DNA bending statistics for small lengths down to one helical turn. The accuracy of experimental estimates could be improved due to a large data volume and a refined algorithm for image processing and measuring bend angles.
View Article and Find Full Text PDFPhys Rev Lett
February 2014
Unusually high bending flexibility has been recently reported for DNA on short length scales. We use atomic force microscopy (AFM) in solution to obtain a direct estimate of DNA bending statistics for scales down to one helical turn. It appears that DNA behaves as a Gaussian chain and is well described by the wormlike chain model at length scales beyond 3 helical turns (10.
View Article and Find Full Text PDFIn aqueous solutions, the helical twist of DNA decreases with temperature. This phenomenon was noticed and studied experimentally several decades ago, but its physical origin remains elusive. The present paper shows that the thermal untwisting can be predicted from the specific properties of the torsional elasticity of the double helix revealed in recent computational studies.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
July 2012
In recent years, significant progress in understanding the properties of supercoiled DNA has been obtained due to nanotechniques that made stretching and twisting of single molecules possible. Quantitative interpretation of such experiments requires accurate knowledge of torques inside manipulated DNA. This paper argues that it is not possible to transfer the entire magnitudes of external torques to the twisting stress of the double helix, and that a reducing torque transfer coefficient (TTC < 1) should always be assumed.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
August 2011
Genomic DNA is constantly subjected to various mechanical stresses arising from its biological functions and cell packaging. If the local mechanical properties of DNA change under torsional and tensional stress, the activity of DNA-modifying proteins and transcription factors can be affected and regulated allosterically. To check this possibility, appropriate steady forces and torques were applied in the course of all-atom molecular dynamics simulations of DNA with AT- and GC-alternating sequences.
View Article and Find Full Text PDFMycoplasmas are the smallest known microorganisms, with drastically reduced genome sizes. One of the essential biochemical pathways lost in mycoplasmas is methylation-mediated DNA repair (MMR), which is responsible for correction of base substitutions, insertions, and deletions in both bacteria and higher organisms. We found that the histone-like protein encoded by the himA/hup_2 gene of Mycoplasma gallisepticum (mgHU) recognizes typical MMR substrates, in contrast to homologues from other species.
View Article and Find Full Text PDFPhys Rev Lett
July 2010
DNA supercoiling plays an important role in a variety of cellular processes. The torsional stress related to supercoiling may also be involved in gene regulation through the local structure and dynamics of the double helix. To check this possibility, steady torsional stress was applied in the course of all-atom molecular dynamics simulations of two DNA fragments with different base pair sequences.
View Article and Find Full Text PDFAn algorithm is developed for modeling atom-level dynamics of DNA subjected to steady external torques. For completeness, simulations with steady stretching loads are also considered. The algorithms were tested in Brownian dynamics simulations of discrete wormlike chain models with calibrated elastic properties to confirm that the elastic responses induced are of desired type and magnitude and that no side effects appear.
View Article and Find Full Text PDFPhys Rev E Stat Nonlin Soft Matter Phys
July 2009
A promising method for measuring intramolecular distances in solution uses small-angle x-ray scattering interference between gold nanocrystal labels [Mathew-Fenn, Science 322, 446 (2008)]. When applied to double-stranded DNA, it revealed that the DNA length fluctuations are strikingly strong and correlated over at least 80 base pair steps. In other words, the DNA behaves as accordion bellows with distant fragments stretching and shrinking concertedly.
View Article and Find Full Text PDFJ Phys Chem B
February 2009
Recent theoretical and experimental studies have suggested that the elastic behavior of the small-length double-helical DNA does not correspond to the simple harmonic model. This article presents a thorough comparison of classical atom-level molecular dynamics (MD) and coarse-grained harmonic approximations. It is shown that the previously predicted duration of MD trajectories necessary for accurate assessment of DNA elasticity was significantly overestimated and that reliable estimates of elastic parameters can be obtained after a few tens of nanoseconds.
View Article and Find Full Text PDFIn recent years, significant progress has been made towards uncovering the physical mechanisms of low-hydration polymorphism in double-helical DNA. The effect appears to be mechanistically similar in different biological systems, and it is due to the ability of water to form spanning H-bonded networks around biomacromolecules via a quasi-two-dimensional percolation transition. In the case of DNA, disintegration of the spanning H-bonded network leads to electrostatic condensation of DNA strands because, below the percolation threshold, water loses its high dielectric permittivity, whereas the concentration of neutralizing counterions becomes high.
View Article and Find Full Text PDFThe paper considers statistical properties of ensembles of chain conformations obtained by short-time Brownian dynamics (BD) of a coarse-grained DNA model in order to find out if the conditions necessary for accurate evaluation of the polymer elasticity are attainable in atom-level molecular dynamics (MD) simulations. To measure the bending persistence length (PL) with a 10% error using data accumulated in a single trajectory of a double helix of 15 base pairs, dynamics should be continued for a few microseconds. However, these estimates should be scaled down by about 2 orders of magnitude because the bending dynamics of short double helices in MD features much smaller relaxation times.
View Article and Find Full Text PDFThe dynamics of ions and water at the surface of DNA are studied by computer simulations in a wide range of hydrations involving the zone of low-hydration polymorphism in DNA. The long-range mobility of ions exhibits a stepwise increase at three distinct hydration levels. The first of them is close to the midpoint of the water percolation transition as well as the midpoint of the transition between A- and B-DNA forms.
View Article and Find Full Text PDFThe probability distributions for bending angles in double helical DNA obtained in all-atom molecular dynamics simulations are compared with theoretical predictions. The computed distributions remarkably agree with the wormlike chain theory and qualitatively differ from predictions of the subelastic chain model. The computed data exhibit only small anomalies in the apparent flexibility of short DNA and cannot account for the recently reported AFM data.
View Article and Find Full Text PDFThe hydrogen-bonded networks of water at the surface of a model DNA molecule are analyzed. At low hydrations, only small water clusters are attached to the DNA surface, whereas, at high hydrations, it is homogeneously covered by a spanning water network. The spanning water network is formed via a percolation transition at an intermediate hydration number of about 15 water molecules per nucleotide, which is very close to the midpoint of polymorphic transitions between A- and B-forms of the double helix.
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