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Science 24 February 1995:
Vol. 267. no. 5201, pp. 1178 - 1183
DOI: 10.1126/science.7855601

Articles

Science, Vol 267, Issue 5201, 1178-1183
Copyright © 1995 by American Association for the Advancement of Science


articles

DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect

CU Kirchgessner, CK Patil, JW Evans, CA Cuomo, LM Fried, T Carter, MA Oettinger, and JM Brown

Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.

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.


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R. Daniel, R. A. Katz, and A. M. Skalka (1999)
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G. C.M. Smith and S. P. Jackson (1999)
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Ku-Dependent Nonhomologous DNA End Joining in Xenopus Egg Extracts.
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OBA/Ku86: DNA Binding Specificity and Involvement in Mammalian DNA Replication.
M. T. Ruiz, D. Matheos, G. B. Price, and M. Zannis-Hadjopoulos (1999)
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J. Immunol. 162, 911-919
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Formation of coding joints in V(D)J recombination-inducible severe combined immune deficient pre-B cell lines.
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J. Biol. Chem. 274, 478-485
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Analysis of variable (diversity) joining recombination in DNAdependent protein kinase (DNA-PK)-deficient mice reveals DNA-PK-independent pathways for both signal and coding joint formation.
M. A. Bogue, C. Jhappan, and D. B. Roth (1998)
PNAS 95, 15559-15564
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Inactivation of DNA-Dependent Protein Kinase by Protein Kinase Cdelta : Implications for Apoptosis.
A. Bharti, S.-K. Kraeft, M. Gounder, P. Pandey, S. Jin, Z.-M. Yuan, S. P. Lees-Miller, R. Weichselbaum, D. Weaver, L. B. Chen, et al. (1998)
Mol. Cell. Biol. 18, 6719-6728
   Abstract »    Full Text »
Failure of Hairpin-Ended and Nicked DNA To Activate DNA-Dependent Protein Kinase: Implications for V(D)J Recombination.
V. Smider, W. K. Rathmell, G. Brown, S. Lewis, and G. Chu (1998)
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Productive and Nonproductive Complexes of Ku and DNA-Dependent Protein Kinase at DNA Termini.
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Requirement for an Interaction of XRCC4 with DNA Ligase IV for Wild-type V(D)J Recombination and DNA Double-strand Break Repair in Vivo.
U. Grawunder, D. Zimmer, P. Kulesza, and M. R. Lieber (1998)
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Xrcc3 Is Required for Assembly of Rad51 Complexes in Vivo.
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J. Biol. Chem. 273, 21482-21488
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A Human Severe Combined Immunodeficiency (SCID) Condition with Increased Sensitivity to Ionizing Radiations and Impaired V(D)J Rearrangements Defines a New DNA Recombination/Repair Deficiency.
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Sequence-specific Binding of Ku Autoantigen to Single-stranded DNA.
H. Torrance, W. Giffin, D. J. Rodda, L. Pope, and R. J. G. Hache (1998)
J. Biol. Chem. 273, 20810-20819
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   Abstract »    Full Text »    PDF »
Structure of Nonhairpin Coding-End DNA Breaks in Cells Undergoing V(D)J Recombination.
M. S. Schlissel (1998)
Mol. Cell. Biol. 18, 2029-2037
   Abstract »    Full Text »
DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139.
E. P. Rogakou, D. R. Pilch, A. H. Orr, V. S. Ivanova, and W. M. Bonner (1998)
J. Biol. Chem. 273, 5858-5868
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Radiation-Induced Chromosome Aberrations in Saccharomyces cerevisiae : Influence of DNA Repair Pathways.
A. A. Friedl, M. Kiechle, B. Fellerhoff, and F. Eckardt-Schupp (1998)
Genetics 148, 975-988
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Lectin Histochemistry Reveals the Appearance of M-cells in Peyer's Patches of SCID Mice After Syngeneic Normal Bone Marrow Transplantation.
R. Sharma, U. Schumacher, and E. Adam (1998)
J. Histochem. Cytochem. 46, 143-148
   Abstract »    Full Text »
DNA-dependent protein kinase: DNA binding and activation in the absence of Ku.
O. Hammarsten and G. Chu (1998)
PNAS 95, 525-530
   Abstract »    Full Text »    PDF »</