Reversion of mutations in the thymidine kinase gene in herpes simplex viruses resistant to phosphonoacetate

Abstract

Mutations in the DNA polymerase locus of phage, bacteria, and eukaryotic cells may change the mutation rates at other loci of the genome. We used resistance to phosphonoacetate to select mutants of herpes simplex virus with mutated DNA polymerase and then determined the reversion frequency of viral thymidine kinase mutation in mutants and recombinants. The results obtained indicate that mutations causing resistance to phosphonoacetate do not affect the mutation rate of the viral genes. This finding is consistent with the existence of two functional regions in the DNA polymerase molecule, one involving the pyrophosphate acceptor site and responsible for resistance to phosphonoacetate and another involved in the editing ability and recognition specificity of the enzyme.