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Nucleic Acids Research, 1985, Vol. 13, No. 23 8623-8630
© 1985

Articles

Differential inhibition of human placental DNA polymerases {delta} and {alpha} by BuPdGTP and BuAdATP

Marietta Y.W.T. Lee*,, N.Lan Toomey and George E. Wright1

Department of Medicine, University of Miami Medical School Miami, FL 33101 1Department of Pharmacology, University of Massachusetts Medical School Worcester, MA 01605, USA

*To whom correspondence should be addressed

Received August 5, 1985. Revised November 6, 1985. Accepted November 6, 1985.

The p-n-butylphenyl- and p-n-butylanilino- substituted analogs of dGTP and dATP, respectively, were tested as inhibitors of purified human placental DNA polymerases {alpha} and {delta}. It was observed that DNA polymerase {alpha} activity was potently inhibited by these analogs with I0.5 values as low as the nanomolar range, whereas DNA polymerase {delta} activity was poorly inhibited, with I0.5 values of ca, 100 micromolar. These results argue for a distinct identity of these two enzymes, and demonstrate the usefulness of these analogs as probes of DNA polymerase structures. In addition, these analogs provide a rapid method for the discrimination of the two enzyme activities and a means for the selective assay of DNA polymerase {delta}. Aphldicolininhibited both DNA polymerases.


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