Differential Incorporation of Thymidylate Analogues into DNA by DNA Polymerase α and by DNA Polymerases Specified by Two Herpes Simplex Viruses Free

Abstract

SUMMARY

Several triphosphates (TP) of 5-substituted deoxyuridine (dU), like 5-ethyl (Et), 5-n-propyl (n-Pr), 5-iso-propyl (iso-Pr), 5-n-hexyl (n-Hx), and 5-trifluorothymidine (F-dT) were used as substrates for polymerase α and for two herpes simplex virus ()-coded polymerases isolated from HeLa cells infected with -1, strain C42 (wild-type), or its mutant resistant to phosphonoformate ( ). All polymerases were purified up to the DNA-cellulose column step and they showed comparable specific activities. The incorporation into DNA studied with all the alkyl analogues of dUTP is several times higher with the virus enzymes than with polymerase α. The polymerase of the mutant virus incorporates dUTP analogues to a lower extent than the wild-type polymerase. The two virus enzymes also differ in the and values for different substrates, indicating that the mutation to PFA has affected the structure of the virus DNA polymerase. Surprisingly, all three enzymes use F-dTTP as substrate for DNA synthesis to an equal but limited extent.

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1982-09-01
2024-03-29
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