Publications by authors named "Alexandr Svidlov"

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.

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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.

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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.

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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.

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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.

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The influence of a single H/H replacement on the frequency generation of different-size bubbles in the human interferon alpha-17 gene (IFNA17) under various energies was studied by a developed algorithm and mathematical modeling without simplifications or averaging. This new approach showed the efficacy of researching DNA bubbles and open states both when all hydrogen bonds in nitrogenous base pairs are protium and after an H-substitution. After a single deuterium substitution under specific energies, it was demonstrated that the non-coding region of IFNA17 had a more significant regulatory role in bubble generation in the whole gene than the promoter had.

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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.

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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.

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