TY - JOUR
T1 - Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination in vivo
AU - Ouyang, Honghai
AU - Nussenzweig, Andre
AU - Kurimasa, Akihiro
AU - Soares, Vera Da Costa
AU - Li, Xiaoling
AU - Cordon-Cardo, Carlos
AU - Li, Wen Hui
AU - Cheong, Nge
AU - Nussenzweig, Michel
AU - Iliakis, George
AU - Chen, David J.
AU - Li, Gloria C.
PY - 1997/9/15
Y1 - 1997/9/15
N2 - 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.
AB - 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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U2 - 10.1084/jem.186.6.921
DO - 10.1084/jem.186.6.921
M3 - Article
C2 - 9294146
AN - SCOPUS:0030885974
SN - 0022-1007
VL - 186
SP - 921
EP - 929
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -