DNA STRUCTURE, REPLICATION AND GENOME VARIABILITY CORRELATION

The study of special features of a new molecular DNA structure synthesis based on the fact that monomers transpositions can occur in the backbone of polymer chains according to the mathematical law known as a Fibonacci numerical series and «the Golden ratio» was performed. The example of the formation of a new DNA model demonstrates that there are dimers of three types in DNA structure: • Dimers with phosphodiester bond P-O-C, [(s-p) + (s-p)]; [(p-s)+(p-s)]; • Dimers with phosphatic bond P-O-P, [(s-p) + (p-s)]; • Dimers with glycosidic bond C-O-C, [(p-s)+(s-p)]. Dimers of the [(s-p) + (p-s)] type are of special importance for the process of replication. For example, if an enzyme catalyst (DNA polymerase) interacts in the backbone of matrix thread with a dimer of [(s-p) + (p-s)] type during the replication process it leads to a thread break. The growth of the daughter thread does not occur until the enzyme catalyst finds the transition point to another matrix thread of DNA, which contains in its backbone monomers similar to those, necessary for the activity of the given DNA polymerase. Thus, during the process of replication the genetic material is redistributed in the cell, and each daughter thread gets the information about genes belonging to both matrix threads of DNA molecule. This pattern of cell genome changing may manifest itself in phenotype or genotype of the body in different ways

Exosome-Mediated Transfer of Cancer Cell Resistance to Antiestrogen Drugs

Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery. The exosomes were purified by differential ultracentrifugation, cell response to tamoxifen was determined by MTT test, and the level and activity of signaling proteins were determined by Western blot and reporter analysis. We found that the treatment of the parent MCF-7 cells with exosomes from the resistant cells within 14 days lead to the partial resistance of the MCF-7 cells to antiestrogen drugs. The primary resistant cells and the cells with the exosome-induced resistance were characterized with these common features: decrease in ERα activity and parallel activation of Akt and AP-1, NF-κB, and SNAIL1 transcriptional factors. In general, we evaluate the established results as the evidence of the possible exosome involvement in the transferring of the hormone/metformin resistance in breast cancer cells