Selection of bacteriophage T4 antimutator DNA polymerases: a link between proofreading and sensitivity to phosphonoacetic acid

Mutat Res. 1996 Feb 19;350(1):9-16. doi: 10.1016/0027-5107(95)00085-2.


During DNA replication, DNA polymerases alternate between DNA synthesis and proofreading the newly synthesized DNA. In order to understand the molecular details of how DNA polymerases determine the balance between polymerase and proofreading activities, it would be useful to have mutants which switch between the two activities either more or less frequently. Antimutator DNA polymerases switch more frequently and thus have more opportunity for proofreading. We have observed that mutant DNA polymerases which proofread less frequently have a mutator phenotype and are inhibited by the pyrophosphate analogue phosphonoacetic acid. Sensitivity to phosphonoacetic acid can be used to isolate second-site suppressor mutations. These suppressor mutations encode amino acid substitutions which produce antimutator DNA polymerases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / genetics
  • Bacteriophage T4 / drug effects
  • Bacteriophage T4 / enzymology
  • Bacteriophage T4 / genetics*
  • Conserved Sequence
  • DNA Replication
  • DNA-Directed DNA Polymerase / genetics*
  • DNA-Directed DNA Polymerase / metabolism
  • Enzyme Inhibitors / pharmacology
  • Mutagenesis*
  • Nucleic Acid Conformation
  • Nucleic Acid Synthesis Inhibitors
  • Nucleotides / metabolism
  • Phenotype
  • Phosphonoacetic Acid / pharmacology*
  • Suppression, Genetic*
  • Temperature
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism


  • Amino Acids
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
  • Nucleotides
  • Viral Proteins
  • gene 43 protein, Enterobacteria phage T4
  • DNA-Directed DNA Polymerase
  • Phosphonoacetic Acid