Ku is a complex of two proteins, Ku70 and Ku80, and functions as a heterodimer to bind DNA double-strand breaks (DSB) and activate DNA-dependent protein kinase. The role of the Ku70 subunit in DNA DSB repair, hypersensitivity to ionizing radiation, and V(D)J recombination was examined in mice that lack Ku70 (Ku70−/−). Like Ku80−/− mice, Ku70−/− mice showed a profound deficiency in DNA DSB repair and were proportional dwarfs. Surprisingly, in contrast to Ku80−/− mice in which both T and B lymphocyte development were arrested at an early stage, lack of Ku70 was compatible with T cell receptor gene recombination and the development of mature CD4+CD8− and CD4−CD8+ T cells. Our data shows, for the first time, that Ku70 plays an essential role in DNA DSB repair, but is not required for TCR V(D)J recombination. These results suggest that distinct but overlapping repair pathways may mediate DNA DSB repair and V(D)J recombination.
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15 September 1997
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September 15 1997
Ku70 Is Required for DNA Repair but Not for T Cell Antigen Receptor Gene Recombination In Vivo
Honghai Ouyang,
Honghai Ouyang
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Andre Nussenzweig,
Andre Nussenzweig
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Akihiro Kurimasa,
Akihiro Kurimasa
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Vera da Costa Soares,
Vera da Costa Soares
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Xiaoling Li,
Xiaoling Li
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Carlos Cordon-Cardo,
Carlos Cordon-Cardo
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Wen-hui Li,
Wen-hui Li
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Nge Cheong,
Nge Cheong
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Michel Nussenzweig,
Michel Nussenzweig
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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George Iliakis,
George Iliakis
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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David J. Chen,
David J. Chen
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Gloria C. Li
Gloria C. Li
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
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Honghai Ouyang
,
Andre Nussenzweig
,
Akihiro Kurimasa
,
Vera da Costa Soares
,
Xiaoling Li
,
Carlos Cordon-Cardo
,
Wen-hui Li
,
Nge Cheong
,
Michel Nussenzweig
,
George Iliakis
,
David J. Chen
,
Gloria C. Li
From the *Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, 10021; ‡Los Alamos National Laboratory, Los Alamos, New Mexico 87545; §Thomas Jefferson University, Philadelphia, Pennsylvania 19107; ‖Rockefeller University, New York, 10021
Address correspondence to G.C. Li, Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave./Box 72, New York, NY 10021. Phone: 212-639-6028; FAX: 212-639-2611; E-mail: [email protected]
The work was supported in part by National Institutes of Health grants CA-31397 and CA-56909 (to G.C. Li), CA-42026 (to G. Iliakis), CA-50519 (to D.J. Chen), and Department of Energy Office of Health and Environmental Research (to D.J. Chen). A. Nussenzweig is a research fellow supported by National Institutes of Health training grant CA61801 and M. Nussenzweig is an associate investigator in the Howard Hughes Medical Institute.
1
Abbreviations used in this paper: AFIGE, asymmetric field inversion gel electrophoresis; CFU-GM, granulocyte/macrophage CFUs; DNA-PK, DNA-dependent protein kinase; DSB, double-strand break, ES, embryonic stem; Gy, Gray; IR, ionizing radiation; IVS, intervening sequence; SP, single-positive.
Received:
May 23 1997
Revision Received:
July 14 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (6): 921–929.
Article history
Received:
May 23 1997
Revision Received:
July 14 1997
Citation
Honghai Ouyang, Andre Nussenzweig, Akihiro Kurimasa, Vera da Costa Soares, Xiaoling Li, Carlos Cordon-Cardo, Wen-hui Li, Nge Cheong, Michel Nussenzweig, George Iliakis, David J. Chen, Gloria C. Li; Ku70 Is Required for DNA Repair but Not for T Cell Antigen Receptor Gene Recombination In Vivo . J Exp Med 15 September 1997; 186 (6): 921–929. doi: https://doi.org/10.1084/jem.186.6.921
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