title: ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage.
abstract: ATM is one of the sentries at the gate of genome stability. This multifunctional protein kinase orchestrates the intricate array of cellular responses to DNA double-strand breaks. Absence or inactivation of ATM leads to the pleiotropic genetic disorder ataxia-telangiectasia (A-T), whose hallmarks are neuronal degeneration, immunodeficiency, genomic instability, premature aging and cancer predisposition. Several features of the complex clinical and cellular phenotype of A-T are reminiscent of other syndromes involving neurodegeneration, premature aging or genomic instability. A common denominator of many of these conditions is the perturbation of the cellular balance of reactive oxygen species, which leads to constant oxidative stress. Of these disorders, ATM deficiency is one of the most extensively studied with regard to the genome instability-oxidative stress connection. This connection may provide new insights into the phenotypes associated with genetic deficiencies of DNA damage responses, and point to new strategies to alleviate some of their clinical symptoms.
authors.affiliation: Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978, Tel Aviv, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Barzilai
authors.forename: Galit
authors.initials: G
authors.lastname: Rotman
authors.forename: Yosef
authors.initials: Y
authors.lastname: Shiloh
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D019457:Chromosome Breakage; D004249:DNA Damage; D004268:DNA-Binding Proteins; D006801:Humans; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency*; D011995:Recombination, Genetic; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases