The herpes simplex virus 1 segment inversion site is specifically cleaved by a virus-induced nuclear endonuclease

Nuclear extracts from several tissue culture cell lines (human, primate, and murine) contain an endonuclease that specifically cleaves sequences at the herpes simplex virus 1 (HSV-1) segment inversion site. Mapping studies identified the preferential site of cleavage as a set of tandemly repeated dodecamers, the DR2 repeats. Endonuclease levels vary according to the proliferative state of the cell; little or no activity is detectable in extracts from quiescent cells, whereas high levels are expressed in dividing cells. Also, infection of density-arrested BSC-1 cells with HSV-1 induces a substantial increase (at least 35-fold) in endonucleolytic activity, which is first detectable at about 1 hr after infection at 32 degrees C. The elevated levels of enzyme activity then persist throughout the viral life cycle. In addition to the HSV-1 DR2 repeats, certain other G+C-rich sequences with an asymmetric distribution of purines and pyrimidines on the DNA strands and with appropriate sequences and lengths are substrates for the nuclease. These data indicate that target site recognition by the enzyme is conformation specific rather than sequence specific.