title: The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species.
abstract: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency radiation sensitivity, and cancer predisposition. A-T heterozygotes are moderately cancer prone. The A-T gene, designated ATM, was recently identified in our laboratory by positional cloning, and a partial cDNA clone was found to encode a polypeptide with a PI-3 kinase domain. We report here the molecular cloning of a cDNA contig spanning the complete open reading frame of the ATM gene. The predicted protein of 3056 amino acids shows significant sequence similarities to several large proteins in yeast, Drosophila and mammals, all of which share the PI-3 kinase domain. Many of these proteins are involved in the detection of DNA damage and the control of cell cycle progression. Mutations in their genes confer a variety of phenotypes with features similar to those observed in human A-T cells. The complete sequence of the ATM gene product provides useful clues to the function of this protein, and furthers understanding of the pleiotropic nature of the A-T mutations.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: K
authors.initials: K
authors.lastname: Savitsky
authors.forename: S
authors.initials: S
authors.lastname: Sfez
authors.forename: D A
authors.initials: DA
authors.lastname: Tagle
authors.forename: Y
authors.initials: Y
authors.lastname: Ziv
authors.forename: A
authors.initials: A
authors.lastname: Sartiel
authors.forename: F S
authors.initials: FS
authors.lastname: Collins
authors.forename: Y
authors.initials: Y
authors.lastname: Shiloh
authors.forename: G
authors.initials: G
authors.lastname: Rotman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004260:DNA Repair; D004268:DNA-Binding Proteins; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human