The molecular mechanism of inhibition of alpha-type DNA polymerases by N2-(butylphenyl)dGTP and 2-(butylanilino)dATP: variation in susceptibility to polymerization

Nucleic Acids Res. 1991 Apr 11;19(7):1627-32. doi: 10.1093/nar/19.7.1627.


Calf thymus DNA polymerase alpha (pol alpha) and bacteriophage T4 DNA polymerase (pol T4) were exploited as model enzymes to investigate the molecular mechanism of inhibitory action of N2-(p-n-butylphenyl)dGTP (BuPdGTP) and 2-(p-n-butyl-anilino)dATP (BuAdATP) on the BuPdNTP-susceptible alpha polymerase family. Kinetic analysis of inhibition of pol alpha with mixtures of complementary and noncomplementary template:primers indicated that both nucleotides induced the formation of a polymerase: inhibitor:primer-template complex. Primer extension experiments using the guanine form as the model analog indicated that pol alpha cannot utilize these nucleotides to extend primer termini. In contrast, pol T4 polymerized BuPdGTP, indicating that resistance to polymerization is not a common feature of the inhibitor mechanism among the broad membership of the alpha polymerase family.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / pharmacology
  • Animals
  • Base Sequence
  • Cattle
  • DNA-Directed DNA Polymerase / genetics
  • Deoxyguanine Nucleotides / pharmacology*
  • Kinetics
  • Molecular Sequence Data
  • Nucleic Acid Synthesis Inhibitors*
  • Polymers*
  • T-Phages / enzymology
  • Templates, Genetic
  • Thymus Gland / enzymology


  • Deoxyguanine Nucleotides
  • Nucleic Acid Synthesis Inhibitors
  • Polymers
  • N(2)-(4-n-butylphenyl)-2'-deoxyguanosine 5'-triphosphate
  • Adenosine Triphosphate
  • 4-n-butylanilino dATP
  • DNA-Directed DNA Polymerase