Abstract
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 (2'-deoxynucleoside-5'-triphosphate: DNA-deoxynucleotidyltransferase, EC 2.7.7.7[EC] ) 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 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 . 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 , but inhibited the DNA polymerase specified by HSV-2.