Catalytic subunit of DNA-dependent protein kinase: Impact on lymphocyte development and tumorigenesis

Akihiro Kurimasa, Honghai Ouyang, Li Jin Dong, Sa Wang, Xiaoling Li, Carlos Cordon-Cardo, David J. Chen, Gloria C. Li

Research output: Contribution to journalArticle

142 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1403-1408
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number4
DOIs
StatePublished - Feb 16 1999

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DNA-Activated Protein Kinase
Catalytic DNA
Catalytic Domain
Carcinogenesis
Lymphocytes
DNA
Aberrant Crypt Foci
T-Cell Lymphoma
Radiation Tolerance
Homologous Recombination
Intestinal Mucosa
Hyperplasia
Hypersensitivity
Joints
Radiation
Phenotype
Growth

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Catalytic subunit of DNA-dependent protein kinase : Impact on lymphocyte development and tumorigenesis. / Kurimasa, Akihiro; Ouyang, Honghai; Dong, Li Jin; Wang, Sa; Li, Xiaoling; Cordon-Cardo, Carlos; Chen, David J.; Li, Gloria C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 4, 16.02.1999, p. 1403-1408.

Research output: Contribution to journalArticle

Kurimasa, Akihiro ; Ouyang, Honghai ; Dong, Li Jin ; Wang, Sa ; Li, Xiaoling ; Cordon-Cardo, Carlos ; Chen, David J. ; Li, Gloria C. / Catalytic subunit of DNA-dependent protein kinase : Impact on lymphocyte development and tumorigenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 4. pp. 1403-1408.
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