Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis Journal Article
| Authors: | Kurimasa, A.; Ouyang, H.; Dong, L. J.; Wang, S.; Li, X.; Cordon-Cardo, C.; Chen, D. J.; Li, G. C. |
| Article Title: | Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis |
| Abstract: | The DNA-dependent protein kinase (DNA-PK) consists of a heterodimer DNA- binding complex, Ku70 and Ku80, and a large catalytic subunit, DNA-PKcs. To examine the role of DNA-PKcs in lymphocyte development, radiation sensitivity, and tumorigenesis, we disrupted the mouse DNA-PKcs by homologous recombination. DNA-PKcs-null mice exhibit neither growth retardation nor a high frequency of T cell lymphoma development, but show severe immunodeficiency and radiation hypersensitivity. In contrast to the Ku70-/- and Ku80-/- phenotype, DNA-PKcs-null mice are blocked for V(D)J coding but not for signal-end joint formation. Furthermore, inactivation of DNA-PKcs leads to hyperplasia and dysplasia of the intestinal mucosa and production of aberrant crypt foci, suggesting a novel role of DNA-PKcs in tumor suppression. |
| Keywords: | dna-binding proteins; exons; nonhuman; flow cytometry; animal cell; mouse; phenotype; animals; mice; mice, knockout; gene; cell survival; complex formation; reverse transcription polymerase chain reaction; cell maturation; embryo; genotype; immunoglobulin; mice, scid; carcinogenesis; animalia; transcription factors; cell transformation, neoplastic; nuclear proteins; t lymphocyte receptor; gene rearrangement; reverse transcriptase polymerase chain reaction; protein-serine-threonine kinases; hyperplasia; immunoblotting; simian virus 40; cell line, transformed; dimerization; tumor; vdj recombinases; intestinal neoplasms; catalytic domain; lymphocyte; immunologic deficiency syndromes; dna helicases; macromolecular substances; enzyme active site; precancerous conditions; radiation tolerance; southern blotting; dna dependent protein kinase; gamma rays; dna nucleotidyltransferases; intestinal mucosa; dna-activated protein kinase; antigens, nuclear; cesium radioisotopes; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 96 |
| Issue: | 4 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1999-02-16 |
| Start Page: | 1403 |
| End Page: | 1408 |
| Language: | English |
| DOI: | 10.1073/pnas.96.4.1403 |
| PUBMED: | 9990036 |
| PROVIDER: | scopus |
| PMCID: | PMC15475 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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132Li -
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Ouyang -
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Wang -
612
Cordon-Cardo -
6
Li
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