Effect of the major DNA adduct of the antitumor drug cis-diamminedichloroplatinum (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-diamminedichloroplatinum(II) on the activity of a helicase known to be essential for DNA replication, we have examined its interaction with the origin-binding protein (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 translocates. This effect was paralleled by a comparable inhibition of the UL9 protein's DNA-dependent ATPase activity. The inhibitory effect of the lesion 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 physical interaction that is known to exist between the UL9 protein and ICP8, and not due to the preferential interaction of ICP8 with the adduct.
Villani
G
G
Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS, Toulouse, France.
Pillaire
M J
MJ
Boehmer
P E
PE
D000251:Adenosine Triphosphatases / Q000187:drug effects; D001483:Base Sequence; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004265:DNA Helicases / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000187:drug effects*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000201:enzymology; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000187:drug effects* / Q000378:metabolism
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D015226:Dinucleoside Phosphates; C045462:ICP8 protein, Simplexvirus; D014764:Viral Proteins; C064565:UL9 protein, Human herpesvirus 1; C034298:deoxyguanylyl-(3'-5')-guanosine; D000251:Adenosine Triphosphatases; D004265:DNA Helicases; D002945:Cisplatin