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. 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.