[Nature of DNA-protein interactions in chromatin. Analysis of the binding sequence of histone fractions with DNA and polyphosphates].
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Biomedical subjects
Publications and source records attributed to D M Spitkovskiĭ.
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A method of fluorescent microscopy with the aid of acridine orange was applied in these studies; some features of the changes in the structure of interphasic chromatin characteristic of their sick children were revealed on the short-term cultures of lymphoyctes obtained from the mothers with children suffering from Down's syndrome. Sibling girls also displayed deviations similar to the changes revealed in their mothers. The data obtained permit to suppose the existence of a definite population of women, peculiarities of whose genotype promoted the appearance on the structural chromatin organization was revealed only in the mothers and sibling girls it is suggested that the mentioned genotype peculiarities were hereditary and connected with genes (or certain chromatin areas) limited by sex.
A thermomechanical method was applied to the study of the interaction of the model desoxyribonucleoprotein systems (DNP-systems) of chromatin with the blood sera of healthy and sick persons. It was demonstrated that the blood sera of healthy persons caused decondensation of the DNP-systems. The intensity of this action varied when the sera with the composition altered as a result of pathology were used: the sera of the patients suffering from systemic lupus erythematosus increased the condensation; in comparison with the sera of healthy persons, the sera of schizophrenic patients intensified the DNP-system decondensation. The sera action was not connected with the activity of the serum enzymes. The role played by the serum components in regulation of the structural-functional chromatin properties is discussed.
By using fluorescent microscopy and acridine orange staining it was shown in the studies on short-term culture of human cells that the melting patterns of chromatin DNA of intact lymphocytes of healthy individuals represented the curves with 6 maxima (F530) at the temperature ranges of 45 degrees C, 65 degrees C, 85 degrees C, and 92 degrees C (P less than 0.01). The melting patterns of lymphocytes from patients with Down's disease represented curves with 4 maxima at the temperature ranges of 65 degrees C, 85 degrees C, 88 degrees C, 92 degrees C (P less than 0.01). No decline in the fluorescence intensity at the temperature intervals of 78 degrees C-85 degrees C was apparently due to a greater degree of condensation of definite regions of the trisomal cell chromatin complex. Possible mechanisms accounting for structural readjustments of the interphasic human lymphocyte chromatin occurring under thermal effects are discussed.
It was shown with the model supramolecular chromatin systems that the activity of the factor of chromatin condensation changes in the process of liver regeneration. No activity of the factor of chromatin condensation was found 20 hrs after operation. Within 32-33 hrs (in the period of increased mitotic frequency) its activity approaches that prior to the operation. The nature of the activity of the factor of chromatin condensation is discussed with respect to the functional state of chromatin.
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Novel biophysical and biological aspects of eukaryotic cell response to low doses of low-LET radiation are considered in the present paper. The model of universal nuclear target in eukaryotic cells is proposed. The target is considered as a spherical volume homogeneously filled of DNA with adjacent water layer. Thickness of water layer equals to diffusion length of hydroxil radicals hitting DNA. Two subregions are proposed of the cellular membrane with different ability to respond to low doses of ionizing radiation. An original mechanism of repair of DNA double strand breaks (dsb) is described. This mechanism suggests directional conformational movement of separate locuses of homological chromosomes through narrow tube ("throat") between specialised nuclear regions. The fluxes of nuclear liquid induce a force which is responsible for highly elastic chromosome deformation and chromosome movement resulting in proximity of homological chromosomes in the throat. Close proximity is required for DNA dsb repair. All of DNA dsbs have to be repaired in low doses range owing to high genomic stability of eukaryotic cells. However, it has been hypothesized an existence of a small subpopulation of cells with unstable genome named as cells of evolutionary or/and ontogenetical reserve (ER or/and OR). Genomic instability is induced in these cells by epigenetic program. This program results in DNA damage mainly in chromosomal "hot spots". As a result new genetic variants are originated. The ability of cell population in vivo to eliminate or not eliminate Er/OR cells determinates individual sensitivity of organism and hence health consequences to low dose radiation exposure.