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 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 k...

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Veröffentlicht in:Cell 1995-03, Vol.80 (5), p.813-823
Hauptverfasser: Blunt, Tracy, Finnie, Nicholas J, Taccioli, Guillermo E, Smith, Graeme C.M, Demengeot, Jocelyne, Gottlieb, Tanya M, Mizuta, Ryushin, Varghese, A.J, Alt, Frederick W, Jeggo, Penny A, Jackson, Stephen P
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Sprache:eng
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Zusammenfassung: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 cs, the catalytic subunit of this enzyme. Furthermore, we demonstrate that yeast artificial chromosomes containing the DNA-PK cs, gene complement both the DNA repair and recombination deficiencies of V3 cells, and we conclude that DNA-PK cs, 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.
ISSN:0092-8674
1097-4172
DOI:10.1016/0092-8674(95)90360-7