-Homologous recombination of DNA double strand breaks was previously found to be protective against apoptosis in tumor cells lacking p53 function. Here, we studied the spatial and temporal relationship between the two processes in a pair of lymphoblastoid cell lines with wild-type or mutant p53 status. Clonogenic assays revealed that p53 mutant WI-L2-NS cells were ~ ten-fold more resistant to X-ray damage than p53 wild type TK6 cells and displayed 2-3 times lower levels of apoptosis 24 h after irradiation. The kinetics of DNA damage and repair after irradiation (5 Gy) were assessed by immunofluorescent staining for g-H2AX and Rad51, and DNA stained with DAPI. Using image analysis in the three (red/green/blue) fluorescence channels we found that repair foci were more prevalent in the p53 mutant radioresistant WI-L2-NS cells at many time points: 2.2 versus 1 per nucleus at 5 min, 3.2 versus 1.6 at 6 h, and 6.1 versus 3.6 at 72 h post-irradiation although the number of repair foci were equal at 24 h (8.8). Furthermore, the average size of foci in TK6 cells was smaller at all times post-irradiation (p<0.001). In contrast to the functional repair foci which were characterised by the co-localisation and high concentration of g-H2AX and Rad51, in pre-apoptotic cell nuclei, foci with greater quantities of g-H2AX relative to Rad51 were prevalent. The g-H2AX-predominant foci colocalized with little or no Rad51 and fused in a pattern typical of apoptotic chromatin. This pattern was seen more often in TK6 cells, where at 6 h the sum area occupied by g-H2AX was seven-fold higher than that of the Rad51 label. In contrast, WI-L2-NS cells displayed approximately equal areas of both components. These data suggest that formation of stable functional repair foci topologically protects the chromatin from relaxation and initiation of apoptotic fragmentation.

Ample adaptive and functional opportunities of a living cell are determined by the complexity of its structural organisation. However, such complexity gives rise to a problem of maintenance of the coherence of inner processes in macroscopic interims and in macroscopic volumes which is necessary to support the structural robustness of a cell. The solution to this problem lies in multidimensional control of the adaptive and functional changes of a cell as well as its self-renewing processes in the context of environmental conditions. Six mechanisms (principles) form the basis of this multidimensional control: regulatory circuits with feedback loops, redundant inner diversity within a cell, multilevel distributed network organisation of a cell, molecular selection within a cell, continuous informational flows and functioning with a reserve of power. In the review we provide detailed analysis of these mechanisms, discuss their specific functions and the role of the superposition of these mechanisms in the maintenance of cell structural robustness in a wide range of environmental conditions.

The effect of plant polyphenolic compounds (PPs) on the viability of human keratinocytes exposed to ultraviolet (UV) radiation of range C (UVС) and the number of single-stranded DNA breaks in the nuclei of these cells was studied. The experimental data obtained indicate that, along with the cytoprotective effect, the addition of silybin and acacetin immediately after the UVC exposure leads to a significant decrease in the number of single-stranded DNA breaks in the nuclei of HaCaT keratinocytes 2 and 5 h after exposure. It was concluded that PPs are able to reduce the destructive effect of UV radiation on skin cells, reducing the number of genetic damage.