DNA polymerase ? proofreads errors made by DNA polymerase ?.

ABSTRACT: During eukaryotic replication, DNA polymerases ? (Pol?) and ? (Pol?) synthesize the leading and lagging strands, respectively. In a long-known contradiction to this model, defects in the fidelity of Pol? have a much weaker impact on mutagenesis than analogous Pol? defects. It has been previously proposed that Pol? contributes more to mutation avoidance because it proofreads mismatches created by Pol? in addition to its own errors. However, direct evidence for this model was missing. We show that, in yeast, the mutation rate increases synergistically when a Pol? nucleotide selectivity defect is combined with a Pol? proofreading defect, demonstrating extrinsic proofreading of Pol? errors by Pol?. In contrast, combining Pol? nucleotide selectivity and Pol? proofreading defects produces no synergy, indicating that Pol? cannot correct errors made by Pol?. We further show that Pol? can remove errors made by exonuclease-deficient Pol? in vitro. These findings illustrate the complexity of the one-strand-one-polymerase model where synthesis appears to be largely divided, but Pol? proofreading operates on both strands.

SUBMITTER: Bulock CR 

PROVIDER: S-EPMC7084062 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature