Mutations in the herpes simplex virus DNA polymerase gene conferring hypersensitivity to aphidicolin.

Abstract

Fourteen mutants known or likely to contain mutations in the herpes simplex virus DNA polymerase gene were examined for their sensitivity to aphidicolin in plaque reduction assays. Eleven of these exhibited some degree of hypersensitivity to the drug; altered aphidicolin-sensitivity correlated with altered sensitivity to the pyrophosphate analog, phosphonoacetic acid. The DNA polymerase specified by one of these mutants, PAAr5, required roughly seven-fold less aphidicolin to inhibit its activity by 50% than did polymerase specified by its parental strain. Mutations responsible for the aphidicolin-hypersensitivity phenotype of PAAr5 were mapped to an 0.8 kbp region in the herpes simplex virus DNA polymerase locus. These data taken together indicate that 1) mutations in the herpes simplex virus DNA polymerase gene can confer altered sensitivity to aphidicolin, 2) that the HSV polymerase is sensitive to aphidicolin in vivo, and 3) that amino acid alterations which affect aphidicolin binding may affect the pyrophosphate exchange-release site as well, suggesting that aphidicolin binds in close proximity to this site.

• Authors: D M Coen, P A Furman, D P Aschman, P A Schaffer
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 11 Issue 15 Pg. 5287-97 (Aug 11 1983) ISSN: 0305-1048 [Print] England
• PMID: 6308578 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Diterpenes
• Aphidicolin
• DNA Polymerase II
• DNA-Directed DNA Polymerase

Topics

• Animals
• Aphidicolin
• Cell Line
• Chlorocebus aethiops
• DNA Polymerase II (antagonists & inhibitors, genetics)
• DNA-Directed DNA Polymerase (genetics)
• Diterpenes (pharmacology)
• Genes (drug effects)
• Genes, Viral (drug effects)
• Kidney
• Mutation
• Simplexvirus (drug effects, enzymology)
• Species Specificity