DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect.
Severe combined immunodeficient (SCID) mice are deficient in a recombination process utilized in both DNA double-strand break repair and in V(D)J recombination. The phenotype of these mice involves both cellular hypersensitivity to ionizing radiation and a lack of B and T cell immunity. The catalytic subunit of DNA-dependent protein kinase, p350, was identified as a strong candidate for the murine gene SCID. Both p350 and a gene complementing the SCID defect colocalize to human chromosome 8q11. Chromosomal fragments expressing p350 complement the SCID phenotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice.
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
C U
CU
Kirchgessner
C K
CK
Patil
J W
JW
Evans
C A
CA
Cuomo
L M
LM
Fried
T
T
Carter
M A
MA
Oettinger
J M
JM
Brown
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D004260:DNA Repair / Q000235:genetics; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005720:Gamma Rays; D005816:Genetic Complementation Test; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance; D011995:Recombination, Genetic; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000235:genetics*
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases