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. 1996 Nov;70(11):7471–7477. doi: 10.1128/jvi.70.11.7471-7477.1996

Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0.

S P Lees-Miller 1, M C Long 1, M A Kilvert 1, V Lam 1, S A Rice 1, C A Spencer 1
PMCID: PMC190814  PMID: 8892865

Abstract

The DNA-dependent protein kinase (DNA-PK) is involved in several fundamental nuclear processes, including DNA double-strand break repair, V(D)J recombination, and transcription by RNA polymerases I and II. In this study, we show that infection of mammalian cells with herpes simplex virus type 1 attenuates DNA-PK activity by specifically depleting the p350/DNA-PKcs catalytic subunit. The half-life of the p350/DNA-PKcs protein decreases from greater than 24 h to less than 4 h following infection. The depletion of DNA-PK activity and p350/DNA-PKcs abundance is dependent on expression of the viral immediate-early protein ICP0. As ICP0 acts as a promoter-independent transactivator of gene expression, these data suggest that ICP0 may function by directly or indirectly targeting the p350/DNA-PKcs subunit of DNA-PK, thereby altering the inhibitory effects of DNA-PK on RNA polymerase II transcription.

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Selected References

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