Proceedings of the National Academy of Sciences · 1979 · 162 citations · 23 references
Life SciencesBiochemistryMolecular BiologyDna ReplicationEnzymologyMicrobial GeneticsDna Polymerase FunctionError-prone MutagenesisMismatch RepairMutation ProcessesPolymerase Chain ReactionReplication FidelityConcentration DependenceDna Polymerase IiiError-prone Dna ReplicationMismatched Base PairsMutationPhage Dna ReplicationPolymerase KineticsProofreading Mechanisms
DNA from phi X174 is replicated in vitro with a fidelity similar to that found genetically. A mutation of TAG leads to TGG may be induced, however, by varying the concentrations of deoxynucleoside triphosphates, with a frequency proportional to [dGTP]2/[dATP]. This complex concentration dependence is consistent with the active participation of a proofreading mechanism that hydrolytically excises mismatched base pairs as they are formed. A simple kinetic analysis predicts that the frequency of misincorporation depends on the ratio of incorrect to correct deoxynucleoside triphosphates times the concentration of the next triphosphate in the sequence to be added. This suggests that spontaneous mutation by misincorporation depends crucially on the composition of the deoxynucleoside triphosphate pool.
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The nucleotide sequence of bacteriophage φX174
Frederick Sanger, Alan Coulson, Theodore Friedmann et al. · Journal of Molecular Biology · 1978 · 694 citations