Peculiarities of Molecular Mechanisms Involved in Modification of the Structural and Molecular Organization of the Cell Genome.

Within the framework of the previously proposed model of structural organization of DNA that supplements the Watson-Crick model and is based on a mathematical regulation - Fibonacci sequence, we suppose the existence of nucleotides without nitrogenous base and acting as linkers connecting DNA subunits.

Changes in the Quantitative Composition of the Population in Delayed Periods After γ-Radiation Exposure of the Cells in Various Phases of S Period of the First Mitotic Cycle.

Using the autoradiographic method, we studied the kinetics of DNA synthesis over the mitotic cycle in mouse corneal epithelium cells in delayed periods after γ-irradiation in different points of the S phase of the first mitotic cycle. The index labeled cells during 1-3 periods of DNA synthesis most adequately reflects quantitative changes in the cell population composition after cell exposure during the first S period. The relative number of labeled S phase cells in the second mitotic cycle in experiments where the cells were irradiated in the S1 phase of the first S period was 4-fold lower than in experiments where the cells were exposed during S2 phase. This effect is determined by inhibition of the transcription factors activation. It seems that two territorially different sites of the genome controlling the regulatory stimuli and involved in modification of the quantitative composition of the population are responsible for changes in its quantitative balance.

Delayed Consequences of Changes in DNA Synthesis in Cells Exposed to Single Irradiation at the End of S Phase of the Mitotic Cycle.

Kinetics of DNA synthesis throughout the mitotic cycle in mouse corneal epithelial cells after single γ-irradiation of cells (4 Gy) at the end of S phase was studied by the method of radioautography. It was found that single irradiation increased the duration of S phase due to reparation of damage in the cell at the expense of time that normally falls on g1 phase. During reparation, two parallel DNA synthesis processes occur in the damaged cells: de novo synthesis at the site of injury after excision of the damaged fragments (reparative synthesis) and supplementary synthesis during the repair period in the remaining undamaged genome competent for replication. During supplementary synthesis, repeats appear in DNA structure, which increases the amount of genetic material in the cell and affect S phase duration. All reparative processes take place in the cell population consisting of subpopulations of "differentiated", "resting", and "proliferating" cells. The changes in the proportions between the subpopulations under the influence of extreme factors can induce the appearance of metastatic cells in the population.