Open AccessThe molecular mechanism of inhibition of alpha-type DNA polymerases by N2-(butylphenyl)dGTP and 2-(butylanilino)dATP: variation in susceptibility to polymerization
Author(s) -
Naseema N. Khan,
George E. Wright,
Neal C. Brown
Publication year - 1991
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/19.7.1627
Subject(s) - dna polymerase , primer (cosmetics) , biology , polymerase , microbiology and biotechnology , processivity , dna polymerase ii , dna clamp , guanine , dna polymerase delta , nucleotide , dna , dna polymerase beta , dna polymerase mu , primer extension , dna polymerase i , biochemistry , polymerase chain reaction , dna repair , base excision repair , circular bacterial chromosome , reverse transcriptase , gene , chemistry , organic chemistry
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.
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