EFFECT OF THE MAJOR DNA ADDUCT OF THE ANTITUMOR DRUG CIS-DIAMINEDICHLOROPLATINUM(II) ON THE ACTIVITY OF A HELICASE ESSENTIAL FOR DNA-REPLICATION, THE HERPES-SIMPLEX VIRUS TYPE-1 ORIGIN-BINDING PROTEIN

To determine the effect of the major DNA adduct, the intrastrand d(GpG ) cross-link, produced by the antitumor drug cis-diamminedichloroplati num(II) on the activity of a helicase known to be essential for DNA re plication, we have examined its interaction with the origin-binding pr otein (UL9 protein) of herpes simplex virus type-1. We found that the helicase activity of the UL9 protein is inhibited only when the adduct is present on the template strand along which the protein translocate s. This effect was paralleled by a comparable inhibition of the UL9 pr otein's DNA-dependent ATPase activity. The inhibitory effect of the le sion can be reduced by the addition of the herpes simplex virus type-1 single-stranded DNA-binding protein, ICP8 This stimulatory effect is specific for ICP8 and appears to be the result of the functional and p hysical interaction that is known to exist between the UL9 protein and ICP8, and not; due to the preferential interaction of ICP8 with the a dduct.