[Cellular repair potential in families of ataxia-telangiectasia patients].

The key protein of the global cellular response to DNA damage is proteinkinase ATM. Ataxia-telangiectasia (AT), a genetic disorder due to mutations in both alleles of ATM gene, is characterized by numerous neurological abnormalities, increased frequency of malignant tumors, premature ageing and increased radio sensitivity. AT is the most frequently found disease displaying inherited radio sensitivity. The data accumulated by this time on the role of the protein ATM in regulation of cellular response to DNA damage and detailed description of its proteins-targets allows to analyze repair potential and manifestation of premature ageing markers both in the cells obtained from AT patients and in the cells of their heterozygous parents. Primary skin fibroblasts obtained from AT patients and their heterozygous parents were analyzed by the flow cytometry and comet assay. It has been shown that cells of the patient AT8SP do not initiate cell cycle blockade after ionizing irradiation during all the experiment, unlike the healthy donor cells where cell cycle blockade is observed. Irradiated cells of the heterozygous parents demonstrated less brightly expressed changes in cell cycle parameters than healthy donor's cells did. The ability to repair DNA double-strand breaks (DSBs) after irradiation is reduced in the cells of AT patients and their heterozygous parents in comparison with the healthy donor's cells. Cells of the healthy donor were capable to repair not less than 90 % of DNA damage for 2.5 h. The repair efficiency in the cells of AT patients came only to about 30 % of DNA damage and in the cells of heterozygous carries of the disease was approximately 50 %. The difference in the dynamics of DNA damage repair process in different proband's families is in accordance with the reports about great phenotypic variety of the given disease.