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Science 23 April 1999:
Vol. 284. no. 5414, pp. 644 - 647
DOI: 10.1126/science.284.5414.644
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Reports

A Role for DNA-PK in Retroviral DNA Integration

René Daniel, Richard A. Katz, Anna Marie Skalka *

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.

Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
*   To whom correspondence should be addressed. E-mail: AM_Skalka{at}fccc.edu

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   Abstract »    Full Text »    PDF »
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A. Lieber, M. A. Kay, and Z.-Y. Li (2000)
J. Virol. 74, 721-734
   Abstract »    Full Text »    PDF »
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Y. Zhu, S. Zou, D. A. Wright, and D. F. Voytas (1999)
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   Abstract »    Full Text »
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J. Virol. 73, 8599-8611
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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E. Brin, J. Yi, A. M. Skalka, and J. Leis (2000)
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   Abstract »    Full Text »    PDF »
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R. A. Katz, P. DiCandeloro, G. Kukolj, and A. M. Skalka (2001)
J. Biol. Chem. 276, 34213-34220
   Abstract »    Full Text »    PDF »
Poly(ADP-ribose) polymerase-1 is required for efficient HIV-1 integration.
H. C. Ha, K. Juluri, Y. Zhou, S. Leung, M. Hermankova, and S. H. Snyder (2001)
PNAS 98, 3364-3368
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