title: A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation.
abstract: The equine SCID defect is more severe than its murine counterpart in that SCID foals are incapable of forming either coding or signal joints, whereas SCID mice manifest normal signal joint formation. To determine the basis of this difference and whether DNA-dependent kinase, catalytic subunit (DNA-PK(CS)), is involved in signal joint formation, equine DNA-PK(CS) transcripts were cloned and sequenced from normal and SCID cell lines. In the mutant allele, a frame-shift mutation truncates the protein N terminal of the domain with homology to the phosphatidylinositol 3-kinase family resulting in complete absence of full length DNA-PK(CS) and accounting for the kinase-negative phenotype of these cells; the mutation in SCID mice allows for some DNA-PK(CS) expression. The difference in DNA-PK(CS) expression in SCID mice and foals explains the more severe phenotype of equine SCID, and definition of DNA-PK(CS) as the defect in equine SCID demonstrates that DNA-PK(CS) is required for both coding and signal joint formation.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: E K
authors.initials: EK
authors.lastname: Shin
authors.forename: L E
authors.initials: LE
authors.lastname: Perryman
authors.forename: K
authors.initials: K
authors.lastname: Meek
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D015321:Gene Rearrangement; D006736:Horses; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D007135:Immunoglobulin Variable Region; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases