A role for DNA-PK in retroviral DNA integration.
Retroviral DNA integration is catalyzed by the viral protein integrase. Here, it is shown that DNA-dependent protein kinase (DNA-PK), a host cell protein, also participates in the reaction. DNA-PK-deficient murine scid cells infected with three different retroviruses showed a substantial reduction in retroviral DNA integration and died by apoptosis. Scid cell killing was not observed after infection with an integrase-defective virus, suggesting that abortive integration is the trigger for death in these DNA repair-deficient cells. These results suggest that the initial events in retroviral integration are detected as DNA damage by the host cell and that completion of the integration process requires the DNA-PK-mediated repair pathway.
Daniel
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R
Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
Katz
R A
RA
Skalka
A M
AM
D000818:Animals; D017209:Apoptosis; D016466:CHO Cells; D002470:Cell Survival; D002478:Cells, Cultured; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics* / Q000502:physiology; D016662:Virus Integration; D014779:Virus Replication
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D019426:Integrases