DEFECTIVE DNA-DEPENDENT PROTEIN-KINASE ACTIVITY IS LINKED TO V(D)J RECOMBINATION AND DNA-REPAIR DEFECTS ASSOCIATED WITH THE MURINE SCID MUTATION

Murine cells homozygous for the severe combined immune deficiency muta tion (scid) and V3 mutant hamster cells fall into the same complementa tion group and show similar defects in V(D)J recombination and DNA dou ble-stranded break repair. Here we show that both cell types lack DNA- dependent protein kinase (DNA-PK) activity owing to defects in DNA-PKc s, the catalytic subunit of this enzyme. Furthermore, we demonstrate t hat yeast artificial chromosomes containing the DNA-PKcs, gene complem ent both the DNA repair and recombination deficiencies of V3 cells, an d we conclude that DNA-PKcs, is encoded by the XRCC7 gene. As DNA-PK b inds to DNA ends and is activated by these structures, our findings pr ovide novel insights into V(D)J recombination and DNA repair processes .