The influence of isotopic H/D exchange on the stability of the CAG tract of the ATXN2 gene at different values ​​of environmental viscosity

Authors

UDC

538.9

EDN

WRDEPF

DOI:

10.31429/vestnik-22-4-62-68

Abstract

Using mathematical modeling, we investigated the stability of the CAG tract of the ATXN2 gene after a single H/D substitution and various environmental viscosities. It was found that increasing viscosity reduces the likelihood of forming open-state zones in the DNA molecule, while decreasing viscosity stimulates dynamic mobility and an increase in the number of open states. A single H/D substitution was shown to promote additional local stabilization of the structure due to a stronger deuterium bond. These results highlight the importance of environmental physical parameters in influencing the conformational stability and dynamics of the DNA molecule.

Keywords:

isotope exchange, deuterium, viscosity, DNA, mathematical model, ATXN2

Funding information

The publication was prepared within the framework of the implementation of the State Task Force of the Southern Scientific Center of the Russian Academy of Sciences for 2025, state registration number 125011700394-5.

Authors info

  • Oksana M. Lyasota

    научный сотрудник лаборатории проблем распределения стабильных изотопов в живых системах Южного научного центра РАН, младший научный сотрудник научно-исследовательской части Кубанского государственного университета

  • Olga A. Leontyeva

    магистрант кафедры физики и информационных систем Кубанского государственного университета, стажер-исследователь лаборатории проблем распределения стабильных изотопов в живых системах Южного научного центра РАН

  • Alexandra D. Rubailo

    бакалавр кафедры физики и информационных систем Кубанского государственного университета

  • Ekaterina V. Barysheva

    канд. мед. наук, доцент кафедры морфологии человека Российского биотехнологического университета

  • Elena A. Kozlova

    бакалавр кафедры физики и информационных систем Кубанского государственного университета

  • Jose Luis Hernandez Caceres

    старший научный сотрудник Кубинского центра нейронаук

References

  1. Dzhimak, S.S., Drobotenko, M.I., Dorohova, A.A., Coarse-grained mathematical models for studying mechanical properties of the DNA. Biophysical Reviews, 2025. DOI: 10.1007/s12551-025-01339-1
  2. Kumar, S., Mishra, G., Statistical mechanics of DNA unzipping under periodic force: scaling behavior of hysteresis loops. Physical Review Letters, 2013, vol. 110, iss. 25, pp. 258102. DOI: 10.1103/PhysRevLett.110.258102
  3. Libbrecht, M.W., Noble, W.S., Machine learning applications in genetics and genomics. Nature Reviews Genetics, 2015, vol. 16, iss. 6, pp. 321–332. DOI: 10.1038/nrg3920
  4. Olson, W.K., Young, R.T., Czapla, L., DNA simulation benchmarks revealed with the accumulation of high-resolution structures. Biophysical Reviews, 2024, vol. 16, iss. 3, pp. 275–284. DOI: 10.1007/s12551-024-01198-2
  5. Fedulova, L.V., Drobotenko, M.I., Dorohova, A.A., Vasilevskaya, E.R., Svidlov, A.A., Chernukha, I.M., Dzhimak, S.S., Genesis of similar collective states in DNA molecules under various viscosity of the medium and external torque. Journal of Biomolecular Structure and Dynamics, 2025. DOI: 10.1080/07391102.2025.2524406
  6. Yakushevich, L.V., Nonlinear DNA Dynamics: A New Model. Physics Letters A, 1989, vol. 136, pp. 413–417. DOI: 10.1016/0375-9601(89)90425-8
  7. Dorohova, A., Lyasota, O., Dzhimak, S., Svidlov, A., Leontyeva, O., Drobotenko, M., Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in the ATXN2 Gene. Biomedicines, 2024, vol. 12, iss. 10, p. 2396. DOI: 10.3390/biomedicines12102396
  8. Butour, J.L., Macquet, J.P., Viscosity, nicking, thermal and alkaline denaturation studies on three classes of DNA-platinum complex. Biochimica et Biophysica Acta, 1981, vol. 653, iss. 3, pp. 305–315. DOI: 10.1016/0005-2787(81)90187-8
  9. Koenig, V.L., Carrier, W.L., Rahn, R.O., Viscosity studies on DNA and the observation of double-stranded and single-stranded breaks in a 40{%} DMSO-phosphate buffer system. International Journal of Biochemistry, 1974, vol. 5, iss. 7–8, pp. 601–611. DOI: 10.1016/0020-711X(74)90022-6
  10. Джимак, С.С., Дроботенко, М.И., Басов, А.А., Свидлов, А.А., Федулова, Л.В., Лясота, О.М., Барышев, М.Г., Математическое моделирование возникновения открытых состояний в молекуле ДНК в зависимости от концентрации дейтерия в окружающей жидкой среде при разных значениях энергии разрыва водородной связи. Доклады Академии наук, 2018, т. 483, № 5, c. 564–566. [Dzhimak, S.S., Drobotenko, M.I., Basov, A.A., Svidlov, A.A., Fedulova, L.V., Lyasota, O.M., Baryshev, M.G., Mathematical modeling of the emergence of open states in the DNA molecule depending on the concentration of deuterium in the surrounding liquid medium at different values of hydrogen bond rupture energy. Doklady Akademii nauk, 2018, vol. 483, iss. 5, pp. 564–566 (in Russian)] DOI: 10.31857/S086956520003310-4
  11. Laffita-Mesa, J.M., Ataxin-2 gene: a powerful modulator of neurological disorders. Neurogenetics, 2021, vol. 22, iss. 3, pp. 209–220. DOI: 10.1097/WCO.0000000000000959
  12. Costa, R.G., Conceic{c} {a}o, A., Matos, C.A., Nobrega, C., The polyglutamine protein ATXN2: from its molecular functions to its involvement in disease. Cell Death and Disease, 2024, vol. 15, p. 415. DOI: 10.1038/s41419-024-06812-5
  13. Douglas, A.G.L., Penetrance and pleiotropy in ATXN2-related amyotrophic lateral sclerosis. European Journal of Human Genetics, 2025, vol. 33, pp. 1093–1095. DOI: 10.1038/s41431-025-01882-1
  14. Pulst, S.M., Spinocerebellar Ataxia Type 2. Seattle, University of Washington, 1998.
  15. Kumar, M., Tyagi, N., Faruq, M., The molecular mechanisms of spinocerebellar ataxias for DNA repeat expansion in disease. Emerging Topics in Life Sciences, 2023, vol. 7, iss. 3, pp. 289–312. DOI: 10.1042/ETLS20230013
  16. Egorova, P.A., Bezprozvanny, I.B., Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2. Neurotherapeutics, 2019, vol. 16, iss. 4, pp. 1050–1073. DOI: 10.1007/s13311-019-00777-6
  17. Sobczak, K., Krzyzosiak, W.J., CAG repeats containing CAA interruptions form branched hairpin structures in spinocerebellar ataxia type 2 transcripts. Journal of Biological Chemistry, 2005, vol. 280, iss. 5, pp. 3898–3910. DOI: 10.1074/jbc.M409984200
  18. Miller, B.R., Parish, C.A., Wu, E.Y., Molecular dynamics study of the opening mechanism for DNA polymerase I. PLOS Computational Biology, 2014, vol. 10, iss. 12, p. e1003961. DOI: 10.1371/journal.pcbi.1003961
  19. Drobotenko, M.I., Velázquez-Pérez, L., Dorohova, A.A., Lyasota, O.M., Hernandez-Caceres, J.L., Rodriguez-Labrada, R., Svidlov, A.A., Leontyeva, O.A., Baryshev, M.G., Nechipurenko, Y.D., Dzhimak, S.S., Genesis of additional open state zones in the extended polyQ tract of the ATXN2 gene depends on its length and interruptions localization. Archives of Biochemistry and Biophysics, 2025, vol. 772, p. 110531. DOI: 10.1016/j.abb.2025.110531
  20. Englander, S.W., Kallenbach, N.R., Heeger, A.J., Krumhansl, J.A., Litwin, S., Soliton-like states for opening in polynucleotide double helices. Ferroelectrics, 1980, vol. 30, iss. 1, pp. 167. DOI: 10.1080/00150198008209510
  21. Дроботенко, М.И., Джимак, С.С., Свидлов, А.А., Басов, А.А., Лясота, О.М., Барышев, М.Г., Математическая модель двухцепочечной молекулы ДНК с учетом открытых состояний. Биофизика, 2018, Т. 63, № 2, c. 258–264. [Drobotenko M.I., Dzhimak S.S., Svidlov A.A., Lyasota O.M., Baryshev M.G., A Mathematical Model for Basepair Opening in a DNA Double Helix. Biophysics, 2018, vol. 63, iss. 2, pp. 177–182 (in Russian)] DOI: 10.1134/S0006350918020069
  22. Svidlov, A.A., Drobotenko, M.I., Basov, A.A., Baryshev, M.G., Dzhimak, S.S., Influence of the 2H/1H Isotope Composition of the Water Environment on the Probability of Denaturation Bubble Formation in a DNA Molecule. Physics of Wave Phenomena, 2021, vol. 29, iss. 2, pp. 180–185. DOI: 10.3103/S1541308X2102014X
  23. Лясота, О.М., Дорохова, А.А., Дроботенко, М.И., Джимак, С.С., Программа для расчета открытых состояний в последовательности ДНК в зависимости от длины тринуклеотидых повторов. Свидетельство о регистрации программы для ЭВМ RU 2025618875, 08.04.2025. Заявка № 2025617199 от 01.04.2025. [Lyasota, O.M., Dorohova, A.A., Drobotenko, M.I., Dzhimak, S.S., Program for calculating open states in the DNA sequence depending on the length of trinucleotide repeats. Certificate of registration of computer program RU 2025618875, 2025. Application № 2025617199 dated 01.04.2025 (in Russian)]
  24. Drobotenko, M.I., Lyasota, O.M., Hernandez-Caceres, J.L., Rodriguez Labrada, R., Svidlov, A.A., Dorohova, А.A., Baryshev, M.G., Nechipurenko, Y.D., Velázquez Pérez, L., Dzhimak, S.S., Abnormal open states patterns in the ATXN2 DNA sequence depends on the CAG repeats length. International Journal of Biological Macromolecules, 2024, vol. 276, iss. 1, p. 133849. DOI: 10.1016/j.ijbiomac.2024.133849

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Issue

Vol. 22 (2025) No. 4

Pages

62-68

Section

Physics

Dates

Submitted

November 10, 2025

Accepted

November 25, 2025

Published

December 2, 2025

How to Cite

[1]
Lyasota, O.M., Leontyeva, O.A., Rubailo, A.D., Barysheva, E.V., Kozlova, E.A., Hernandez Caceres, J.L., The influence of isotopic H/D exchange on the stability of the CAG tract of the ATXN2 gene at different values ​​of environmental viscosity. Ecological Bulletin of Research Centers of the Black Sea Economic Cooperation, 2025, т. 22, № 4, pp. 62–68. DOI: 10.31429/vestnik-22-4-62-68

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Copyright (c) 2025 Лясота О.М., Леонтьева О.А., Рубайло А.Д., Барышева Е.В., Козлова Е.А., Эрнандес Касерес Х.Л.

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