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Replicative DNA polymerase mutations in cancer
1 2,3
Ellen Heitzer and Ian Tomlinson
Three DNA polymerases — Pol a, Pol d and Pol e — are [1,2]. These enzymes catalyse the polymerisation of
essential for DNA replication. After initiation of DNA synthesis deoxyribonucleotides into the nascent DNA strand.
by Pol a, Pol d or Pol e take over on the lagging and leading While Pol a initiates DNA synthesis, Pol d and Pol e
strand respectively. Pol d and Pol e perform the bulk of replace Pol a after primer extension and perform the bulk
replication with very high fidelity, which is ensured by of DNA replication. Most polymerases lack intrinsic
0
Watson–Crick base pairing and 3 exonuclease (proofreading) error-checking activity, relying on Watson–Crick base
activity. Yeast models have shown that mutations in the pairing for their fidelity. However, the proofreading (exo-
exonuclease domain of Pol d and Pol e homologues can nuclease) domains of Pol d and Pol e ensure that these
cause a mutator phenotype. Recently, we identified germline polymerases have a particularly low error rate, of the order