Telomere-mediated Genomic Instability in Cells from Ataxia Telangiectasia Patients

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Ataxia Telangiectasia Mutated Protein (ATM) is one of the first DNA damage sensors and is involved in telomere repair. Telomeres help maintain the stability of our chromosomes by protecting their ends from degradation. AT patients lacking the gene ATM are susceptible to acquire chromosomal anomalies and show heightened susceptibility to cancer. Here we show that cells from AT patients display considerable telomere attrition. Further, induced DNA damage and genomic instability were found to be more in DNA repair deficient ATM^-/- cells (treated and untreated) than in normal cells. Results demonstrate that the cells ATM- deficient (heterozygous and homozygous) cells are sensitive to arsenite- and radiation-induced oxidative stress. Elevated numbers of chromosome alterations was seen in arsenic-treated and irradiated ATM^-/- cells. The results might help in understanding the extent of susceptibility of AT patients to oxidative stress.