title: The murine DNA-PKcs gene consists of 86 exons dispersed in more than 250 kb.
abstract: The DNA-PKcs gene encodes the 465-kDa catalytic subunit of DNA-dependent protein kinase (DNA-PK), which associates with heterodimeric autoantigens Ku70 and Ku80 and exhibits protein kinase activity depending on DNA double-strand breaks. The gene is also responsible for the aberration in severe combined immune deficiency (SCID) mice, which exhibit a high sensitivity to ionizing radiation and abnormal DNA rearrangement of immunoglobulin and T cell receptor genes. There is further evidence that DNA-PKcs phosphorylates various proteins involved in DNA replication, transcription, repair, and recombination. Nevertheless the structure/function relationship in this huge molecule is virtually unknown. We determined the exons and introns of the murine DNA-PKcs gene by the long-distance polymerase chain reaction method. The murine DNA-PKcs gene consists of 86 exons distributed in a region of more than 250 kb. The average size of the exons is 140 bp. All the splicing sites conform to the GT/AG rule. The SCID mutation site (Tyr4046) has been identified in exon 85. The genomic structure of the DNA-PKcs gene provides clues for the study of various functional domains in this macromolecule.
authors.affiliation: Division of Biology and Oncology, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Fujimori
authors.forename: R
authors.initials: R
authors.lastname: Araki
authors.forename: R
authors.initials: R
authors.lastname: Fukumura
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: K
authors.initials: K
authors.lastname: Mita
authors.forename: K
authors.initials: K
authors.lastname: Tatsumi
authors.forename: M
authors.initials: M
authors.lastname: Abe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005091:Exons; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C497264:Prkdc protein, mouse; D017346:Protein Serine-Threonine Kinases