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Nucleotide selection and pyrophosphate exchange in DNA synthesis: A new proof-reading mechanism

par Lecomte, Philippe;Doubleday, Olivier ;Radman, Miroslaw
Référence Mutation Research, 96, 1, page (139-140)
Publication Publié, 1982

Article révisé par les pairs

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Résumé :

DNA polymerases apparently select and incorporate correct nucleotides but still may make errors in DNA synthesis. However, since the incorrect terminal nucleotides at the growing end of the new DNA chains are poor primers for the continuing DNA polymerization, they have a high probability of being removed by the polymerase-associated 3' → 5' exonuclease activity, which therefore performs a proofreading function. The molecular basis of the initial nucleotide selection, which is defined as all discriminatory processes occurring before the establishment of the new phosphodiester bond, is obscure. Nucleotide selection must be a major contributor to the accuracy of DNA synthesis and to the prevention of radiation-induced mutagenesis, because: exonuclease-free DNA polymerases from mammalian cells still show a high accuracy in vitro, and the absence or inhibition of the proofreading exonuclease is not sufficient to allow erroneous replication of DNA templates damaged by radiations. We shall present arguments for the existence of a proofreading mechanism operating in all replicative enzymes as a part of nucleotide selection, which is associated with pyrophosphate exchange.