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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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J. Virol. 75, 9896-9908
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Characterization of Retrovirus-Host DNA Junctions in Cells Deficient in Nonhomologous-End Joining.
K. Taganov, R. Daniel, R. A. Katz, O. Favorova, and A. M. Skalka (2001)
J. Virol. 75, 9549-9552
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Specific Inhibition of Human Immunodeficiency Virus Type 1 (HIV-1) Integration in Cell Culture: Putative Inhibitors of HIV-1 Integrase.
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R. Daniel, S. Litwin, R. A. Katz, and A. M. Skalka (2001)
J. Virol. 75, 3121-3128
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PNAS
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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
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R. Daniel, R. A. Katz, G. Merkel, J. C. Hittle, T. J. Yen, and A. M. Skalka (2001)
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M. L. Holmes-Son and S. A. Chow (2000)
J. Virol. 74, 11548-11556
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Repair of Gaps in Retroviral DNA Integration Intermediates.
K. E. Yoder and F. D. Bushman (2000)
J. Virol. 74, 11191-11200
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DNA-Dependent Protein Kinase Is Not Required for Efficient Lentivirus Integration.
V. Baekelandt, A. Claeys, P. Cherepanov, E. De Clercq, B. De Strooper, B. Nuttin, and Z. Debyser (2000)
J. Virol. 74, 11278-11285
   Abstract »    Full Text »
Synthesis of Virus-Specific High-Mobility DNA after Temperature Upshift of SC-1 Cells Chronically Infected with Moloney Murine Leukemia Virus Mutant ts1.
P. F. Szurek and B. R. Brooks (2000)
J. Virol. 74, 7055-7063
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High-level expression of active HIV-1 integrase from a synthetic gene in human cells.
P. CHEREPANOV, W. PLUYMERS, A. CLAEYS, P. PROOST, E. DE CLERCQ, and Z. DEBYSER (2000)
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   Abstract »    Full Text »
Identification of Critical Amino Acid Residues in Human Immunodeficiency Virus Type 1 IN Required for Efficient Proviral DNA Formation at Steps prior to Integration in Dividing and Nondividing Cells.
N. Tsurutani, M. Kubo, Y. Maeda, T. Ohashi, N. Yamamoto, M. Kannagi, and T. Masuda (2000)
J. Virol. 74, 4795-4806
   Abstract »    Full Text »
Nuclear Import of Moloney Murine Leukemia Virus DNA Mediated by Adenovirus Preterminal Protein Is Not Sufficient for Efficient Retroviral Transduction in Nondividing Cells.
A. Lieber, M. A. Kay, and Z.-Y. Li (2000)
J. Virol. 74, 721-734
   Abstract »    Full Text »
Tagging chromatin with retrotransposons: target specificity of the Saccharomyces Ty5 retrotransposon changes with the chromosomal localization of Sir3p and Sir4p.
Y. Zhu, S. Zou, D. A. Wright, and D. F. Voytas (1999)
Genes & Dev. 13, 2738-2749
   Abstract »    Full Text »
Initial Binding of Murine Leukemia Virus Particles to Cells Does Not Require Specific Env-Receptor Interaction.
M. Pizzato, S. A. Marlow, E. D. Blair, and Y. Takeuchi (1999)
J. Virol. 73, 8599-8611
   Abstract »    Full Text »    PDF »
Involvement of DNA End-Binding Protein Ku in Ty Element Retrotransposition.
J. A. Downs and S. P. Jackson (1999)
Mol. Cell. Biol. 19, 6260-6268
   Abstract »    Full Text »    PDF »
Degradation of HIV-1 Integrase by the N-end Rule Pathway.
L. C. F. Mulder and M. A. Muesing (2000)
J. Biol. Chem. 275, 29749-29753
   Abstract »    Full Text »    PDF »
Modeling the Late Steps in HIV-1 Retroviral Integrase-catalyzed DNA Integration.
E. Brin, J. Yi, A. M. Skalka, and J. Leis (2000)
J. Biol. Chem. 275, 39287-39295
   Abstract »    Full Text »    PDF »
Role of DNA End Distortion in Catalysis by Avian Sarcoma Virus Integrase.
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
   Abstract »    Full Text »    PDF »
Effect Of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle.
S. Song, P. J. Laipis, K. I. Berns, and T. R. Flotte (2001)
PNAS 98, 4084-4088
   Abstract »    Full Text »    PDF »


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