Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination In vivo.
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.
Ouyang
H
H
Department of Medical Physics and Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
Nussenzweig
A
A
Kurimasa
A
A
Soares
V C
VC
Li
X
X
Cordon-Cardo
C
C
Li
W h
Wh
Cheong
N
N
Nussenzweig
M
M
Iliakis
G
G
Chen
D J
DJ
Li
G C
GC
D000818:Animals; D034961:Antigens, Nuclear; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D004247:DNA / Q000235:genetics; D004265:DNA Helicases; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015329:Gene Rearrangement, T-Lymphocyte; D018390:Gene Targeting; D000072200:Ku Autoantigen; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D034961:Antigens, Nuclear; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D004247:DNA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen