TY - JOUR
T1 - Catalytic subunit of DNA-dependent protein kinase
T2 - Impact on lymphocyte development and tumorigenesis
AU - Kurimasa, Akihiro
AU - Ouyang, Honghai
AU - Dong, Li Jin
AU - Wang, Sa
AU - Li, Xiaoling
AU - Cordon-Cardo, Carlos
AU - Chen, David J.
AU - Li, Gloria C.
PY - 1999/2/16
Y1 - 1999/2/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033574001&partnerID=8YFLogxK
U2 - 10.1073/pnas.96.4.1403
DO - 10.1073/pnas.96.4.1403
M3 - Article
C2 - 9990036
AN - SCOPUS:0033574001
SN - 0027-8424
VL - 96
SP - 1403
EP - 1408
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -