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 het erodimer to bind DNA double-strand breaks (DSB) and activate DNA-depen dent protein kinase. The role of the Ku70 subunit in DNA DSB repair, h ypersensitivity to ionizing radiation, and V(D)J recombination was exa mined in mice that lack Ku70 (Ku70(-/-)). Like Ku80(-/-) mice, Ku70(-/ -) mice showed a profound deficiency in DNA DSB repair and were propor tional dwarfs. Surprisingly, in contrast to Ku80(-/-) mice in which bo th T and B lymphocyte development were arrested at an early stage, lac k of Ku70 was compatible with T cell receptor gene recombination and t he development of mature CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Our da ta 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 re sults suggest that distinct but overlapping repair pathways may mediat e DNA DSB repair and V(D)J recombination.