ATTENUATION OF DNA-DEPENDENT PROTEIN-KINASE ACTIVITY AND ITS CATALYTIC SUBUNIT BY THE HERPES-SIMPLEX VIRUS TYPE-1 TRANSACTIVATOR ICP0

The DNA-dependent protein kinase (DNA-PK) is involved in several funda mental nuclear processes, including DNA double-strand break repair, V( D)J recombination, and transcription by RNA polymerases I and II. In t his study, we show that infection of mammalian cells with herpes simpl ex virus type 1 attenuates DNA-PK activity by specifically depleting t he 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 i nfection. 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 express ion, these data suggest that ICP0 may function by directly or indirect ly targeting the p350/DNA-PKcs subunit of DNA-PK thereby altering the inhibitory effects of DNA-PK on RNA polymerase II transcription.