Differential Substrate Specificity of DNA Polymerase β and of a DNA Polymerase Induced by Herpes Simplex Virus Type 2 towards Thymidine Triphosphate Analogues

Several triphosphates of 5-substituted deoxyuridine (dU), such as 5-ethyl-, 5-n-propyl-, 5-n-hexyl- and 5-isopropyldeoxyuridine triphosphates and 5-trifluorothymidine triphosphate are substrates for HeLa cell DNA polymerase β (2′-deoxynucleoside-5′-triphosphate: DNA-deoxynucleotidyltransferase, EC 2.7.7.7) and for a DNA polymerase isolated from HeLa cells infected with herpes simplex virus type 2 (HSV-2) strain 75. At the concentration tested (50 µm), all these analogues were incorporated more readily into DNA by the virus-coded enzyme than by DNA polymerase β from the host cell. The DNA polymerase coded by HSV-2 showed an affinity for deoxythymidine triphosphate (dTTP) and the analogues studied higher than that of DNA polymerase β. Analogues are preferential substrates for the viral enzyme, since they readily substitute for dTTP during synthesis in vitro. In contrast, arabinosylthymine-5′-triphosphate was readily incorporated into DNA by the host cell DNA polymerase β, but inhibited the DNA polymerase specified by HSV-2.