Defective DNA-dependent protein kinase activity is linked to V (D) J recombination and DNA repair defects associated with the murine scid mutation

T Blunt, NJ Finnie, GE Taccioli, GCM Smith… - Cell, 1995 - cell.com
T Blunt, NJ Finnie, GE Taccioli, GCM Smith, J Demengeot, TM Gottlieb, R Mizuta…
Cell, 1995cell.com
Murine cells homozygous for the severe combined immune deficiency mutation (scid) and
V3 mutant hamster cells fall into the same complementation group and show similar defects
in V (D) J recombination and DNA double-stranded break repair. Here we show that both
cell types lack DNA-dependent protein kinase (DNA-PK) activity owing to defects in DNA-
PK~ s, the catalytic subunit of this enzyme. Furthermore, we demonstrate that yeast artificial
chromosomes containing the DNA-PK~ s gene complement both the DNA repair and …
Summary
Murine cells homozygous for the severe combined immune deficiency mutation (scid) and V3 mutant hamster cells fall into the same complementation group and show similar defects in V (D) J recombination and DNA double-stranded break repair. Here we show that both cell types lack DNA-dependent protein kinase (DNA-PK) activity owing to defects in DNA-PK~ s, the catalytic subunit of this enzyme. Furthermore, we demonstrate that yeast artificial chromosomes containing the DNA-PK~ s gene complement both the DNA repair and recombination deficiencies of V3 cells, and we conclude that DNA-PK~ s is encoded by the XRCC7 gene. As DNA-PK binds to DNA ends and is activated by these structures, our findings provide novel insights into V (D) J recombination and DNA repair processes.
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