title: ATM: from gene to function.
abstract: The identification of ATM , the gene responsible for the pleiotropic recessive disease ataxia telangiectasia, has initiated extensive research to determine the functions of its multifaceted protein product. The ATM protein belongs to a family of protein kinases that share similarities at their C-terminal region with the catalytic domain of phosphatidylinositol 3-kinases. Studies with ataxia telangiectasia (A-T) cells and Atm-deficient mice have shown that ATM is a key regulator of multiple signaling cascades which respond to DNA strand breaks induced by damaging agents or by normal processes, such as meiotic or V(D)J recombination. These responses involve the activation of cell cycle checkpoints, DNA repair and apoptosis. Other roles outside the cell nucleus might be carried out by the cytoplasmic fraction of ATM. In addition, ATM appears to function as a 'caretaker', suppressing tumorigenesis in specific T cell lineages.
authors.affiliation: Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel. grotman@ccsg.tau.ac.il
authors.forename: G
authors.initials: G
authors.lastname: Rotman
authors.forename: Y
authors.initials: Y
authors.lastname: Shiloh
mesh_terms: D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000503:physiopathology; D064007:Ataxia Telangiectasia Mutated Proteins; D020134:Catalytic Domain / Q000235:genetics; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009374:Neoplasms, Experimental / Q000209:etiology; D009410:Nerve Degeneration / Q000235:genetics; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D011836:Radiation Tolerance / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases