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 journalArticlepeer-review

150 Scopus citations

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

ASJC Scopus subject areas

  • General

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