Department of Biochemistry and Molecular Pharmacology
Adenosine Triphosphate; Animals; Base Sequence; Cattle; DNA-Directed DNA Polymerase; Deoxyguanine Nucleotides; Kinetics; Molecular Sequence Data; *Polymers; T-Phages; Templates, Genetic; Thymus Gland
Life Sciences | Medicine and Health Sciences
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.
Nucleic Acids Res. 1991 Apr 11;19(7):1627-32.
Nucleic acids research
Khan, Naseema N.; Wright, George E.; and Brown, Neal C., "The molecular mechanism of inhibition of alpha-type DNA polymerases by N2-(butylphenyl)dGTP and 2-(butylanilino)dATP: variation in susceptibility to polymerization" (1991). Open Access Articles. 1711.