Genesis of additional open state zones in the extended polyQ tract of the ATXN2 gene depends on its length and interruptions localization.

The ATXN2 gene is located on chromosome 12q24.1 and encodes the ataxin-2 protein, which is involved in the regulation of RNA metabolism, protein synthesis, and intracellular signaling. The polyQ tract encoding glutamine can expand, which leads to the development of various neurodegenerative diseases.

Genesis of similar collective states in DNA molecules under various viscosity of the medium and external torque.

The nucleotide sequence determines the structural properties of B-DNA; this fact is considered key in recognizing protein binding sites and changing its activity. Our study has established that, using an angular mathematical model, it is possible to determine areas of similar collective states and bends in the nucleotide sequence that arise even under small torque influences. Calculations were performed for two genes that differ slightly in length ( and fragment of the gene to compare).

Localization of Potential Energy in Hydrogen Bonds of the Gene.

It is known that a number of neurodegenerative diseases, also called diseases of waiting, are associated with the expansion of the polyQ tract in the first exon of the gene. In the expanded polyQ tract, the probability of occurrence of non-canonical configurations (hairpins, G-quadruplexes, etc.) is significantly higher than in the normal one.

Ratio of AT and GC Pairs in the Zones of Open States Genesis in DNA Molecules.

Background: There is an assumption about the presence of a specific nucleotides sequence in DNA molecule, which contributes to the genesis of open states (OS). In addition, it would be logical to assume that OS zones should form in DNA regions with a large proportion of Adenine-Thymine (AT) pairs, since they contain fewer hydrogen bonds than Guanine- Cytosine (GC) base pairs. However, studies have shown that in areas rich in AT pairs, the probability of open states will not always be higher.

Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in the Gene.

Trinucleotide repeats are the cause of many neurodegenerative diseases that are currently incurable. In this regard, the question of the causes of occurrence and methods of prevention or treatment of diseases caused by the expansion of repeats in the CAG tract of the gene remains relevant. Previously, it was shown that the frequency of occurrence of additional OS (open states) zones increases with increasing length of the CAG tract, and the value inverse to the frequency correlates with the age of disease onset.

Stability of the CAG Tract in the Gene Depends on the Localization of CAA Interruptions.

It is known that the presence of CAA codons in the CAG tract affects the nature and time of disease onset caused by the expansion of trinucleotide repeats. The mechanisms leading to the occurrence of these diseases should be sought not only at the level of the physiological role of the protein, but also at the DNA level. These mechanisms are associated with non-canonical configurations (hairpins) that can form in the CAG tract.

Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length.

Hereditary ataxias are one of the «anticipation diseases» types. Spinocerebral ataxia type 2 occurs when the number of CAG repeats in the coding region of the ATXN2 gene exceeds 34 or more. In healthy people, the CAG repeat region in the ATXN2 gene usually consists of 22-23 CAG trinucleotides.

Medium viscosity influence on the open states genesis in a DNA molecule.

The studies were carried out by the mathematical modeling of DNA mechanical deformations. Numerical calculations done for the interferon alpha 17 gene, which consists of 980 base pairs. It has been established that the genesis and dynamics of open states in the DNA molecule depends on the magnitude of the external influence (torque) and on the viscosity of the environment.

Influence of Single Deuterium Replacement on Frequency of Hydrogen Bond Dissociation in IFNA17 under the Highest Critical Energy Range.

The effect of single substitutions of protium for deuterium in hydrogen bonds between pairs of nitrogenous bases on the open states occurrence probability at high critical breaking energies of these bonds has been studied. The study was carried out using numerical methods based on the angular mathematical model of DNA. The IFNA17 gene was divided into three approximately equal parts.

Genesis of Open States Zones in a DNA Molecule Depends on the Localization and Value of the Torque.

The formation and dynamics of the open states in a double-stranded DNA molecule are largely determined by its mechanical parameters. The main one is the torque. However, the experimental study of DNA dynamics and the occurrence of open states is limited by the spatial resolution of available biophysical instruments.

Influence of Environmental Parameters on the Stability of the DNA Molecule.

Fluctuations in viscosity within the cell nucleus have wide limits. When a DNA molecule passes from the region of high viscosity values to the region of low values, open states, denaturation bubbles, and unweaving of DNA strands can occur. Stabilization of the molecule is provided by energy dissipation-dissipation due to interaction with the environment.

DNA Dynamics under Periodic Force Effects.

The sensitivity of DNA to electromagnetic radiation in different ranges differs depending on various factors. The aim of this study was to examine the molecular dynamics of DNA under the influence of external periodic influences with different frequencies. In the present paper, within the framework of a mechanical model without simplifications, we investigated the effect of various frequencies of external periodic action in the range from 10 s to 10 s on the dynamics of a DNA molecule.

Inequality in the Frequency of the Open States Occurrence Depends on Single H/H Replacement in DNA.

In the present study, the effect of H/H isotopic exchange in hydrogen bonds between nitrogenous base pairs on occurrence and open states zones dynamics is investigated. These processes are studied using mathematical modeling, taking into account the number of open states between base pairs. The calculations of the probability of occurrence of open states in different parts of the gene were done depending on the localization of the deuterium atom.