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

doi:10.1073/pnas.96.4.1403

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 journal › Article › peer-review

168 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 language	English
Pages (from-to)	1403-1408
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	96
Issue number	4
DOIs	https://doi.org/10.1073/pnas.96.4.1403
State	Published - 16 Feb 1999
Externally published	Yes

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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.",

author = "Akihiro Kurimasa and Honghai Ouyang and Dong, \{Li Jin\} and Sa Wang and Xiaoling Li and Carlos Cordon-Cardo and Chen, \{David J.\} and Li, \{Gloria C.\}",

year = "1999",

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doi = "10.1073/pnas.96.4.1403",

language = "English",

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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 - https://www.scopus.com/pages/publications/0033574001

U2 - 10.1073/pnas.96.4.1403

DO - 10.1073/pnas.96.4.1403

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SN - 0027-8424

VL - 96

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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 -

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

Abstract

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