ATM is a large, homeostatic protein kinase with roles in various branches of cellular metabolism. ATM’s best characterized function is mobilizing a highly complex network of signaling pathways in response to double-strand breaks (DSBs) in the DNA. DSBs markedly enhance the protein kinase activity of ATM, which subsequently phosphorylates a multitude of substrates, typically key players in the numerous branches of the DNA damage response. ATM is missing or inactive in patients with the multisystem genetic disorder, ataxia telangiectasia (A-T), characterized by neurodegeneration, immune deficiency, genomic instability, sensitivity to ionizing radiation, and cancer predisposition. The cellular phenotype of cells from A-T patients includes premature senescence, chromosomal instability, extreme sensitivity to DSB-inducing agents such as ionizing radiation and radiomimetic chemicals, and defective activation of the extensive DSB...
KeywordsMantle Cell Lymphoma Meiotic Recombination Ataxia Telangiectasia Ataxia Telangiectasia Genotoxic Stress
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