Autor: |
Lyasota O; Department of Biologically Active Substances, Kuban State University, 350040 Krasnodar, Russia.; Laboratory of Problems of Stable Isotope Spreading in Living Systems, Southern Scientific Center of the Russian Academy of Sciences, 344006 Rostov-on-Don, Russia., Dorohova A; Department of Biologically Active Substances, Kuban State University, 350040 Krasnodar, Russia.; Laboratory of Problems of Stable Isotope Spreading in Living Systems, Southern Scientific Center of the Russian Academy of Sciences, 344006 Rostov-on-Don, Russia., Hernandez-Caceres JL; Neurodevelopment Branch, Cuban Center for Neurosciences, Havana 11600, Cuba., Svidlov A; Laboratory of Problems of Stable Isotope Spreading in Living Systems, Southern Scientific Center of the Russian Academy of Sciences, 344006 Rostov-on-Don, Russia., Tekutskaya E; Laboratory of Problems of Stable Isotope Spreading in Living Systems, Southern Scientific Center of the Russian Academy of Sciences, 344006 Rostov-on-Don, Russia., Drobotenko M; Department of Biologically Active Substances, Kuban State University, 350040 Krasnodar, Russia., Dzhimak S; Laboratory of Problems of Stable Isotope Spreading in Living Systems, Southern Scientific Center of the Russian Academy of Sciences, 344006 Rostov-on-Don, Russia.; Department of Radiophysics and Nanotechnology, Kuban State University, 350040 Krasnodar, Russia. |
Abstrakt: |
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 ATXN2 protein, but also at the DNA level. These mechanisms are associated with non-canonical configurations (hairpins) that can form in the CAG tract. The tendency of hairpins to slide along the corresponding threads is usually considered important to explain the expansion of the CAG tract. At the same time, hairpins occur in areas of open states. Previous studies on the role of CAA interruptions have suggested that, under certain conditions, they can stabilize the dynamics of the hairpin, preventing the expansion of the CAG tract. We calculated the probability of additional open state zones occurrence in the CAG tract using an angular mathematical model of DNA. The calculations made it possible to establish that CAA interruptions affect the stability of the CAG tract, and this influence, depending on the localization of the interruption, can both increase and decrease the stability of the CAG tract. |