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

Susan P. Lees-Miller, Melissa C. Long, M. Alison Kilvert, Vivian Lam, Stephen A. Rice, Charlotte A. Spencer

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7471-7477
Number of pages7
JournalJournal of virology
Volume70
Issue number11
DOIs
StatePublished - Nov 1996

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