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• W4200329554 endingPage "1028" @default.
• W4200329554 startingPage "1020" @default.
• W4200329554 abstract "Accurate DNA replication of an undamaged template depends on polymerase selectivity for matched nucleotides, exonucleolytic proofreading of mismatches, and removal of remaining mismatches via DNA mismatch repair (MMR). DNA polymerases (Pols) δ and ε have 3′–5′ exonucleases into which mismatches are partitioned for excision in cis (intrinsic proofreading). Here we provide strong evidence that Pol δ can extrinsically proofread mismatches made by itself and those made by Pol ε, independently of both Pol δ’s polymerization activity and MMR. Extrinsic proofreading across the genome is remarkably efficient. We report, with unprecedented accuracy, in vivo contributions of nucleotide selectivity, proofreading, and MMR to the fidelity of DNA replication in Saccharomyces cerevisiae. We show that extrinsic proofreading by Pol δ improves and balances the fidelity of the two DNA strands. Together, we depict a comprehensive picture of how nucleotide selectivity, proofreading, and MMR cooperate to achieve high and symmetrical fidelity on the two strands. Genetic and genomic analyses show that S. cerevisiae DNA polymerase δ extrinsically proofreads for errors by polymerase ε and itself, and demonstrate that the symmetry of replication fidelity is achieved via coordinated efforts of intrinsic and extrinsic proofreading and DNA mismatch repair." @default.
• W4200329554 created "2021-12-31" @default.
• W4200329554 creator A5004079513 @default.
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• W4200329554 creator A5072131585 @default.
• W4200329554 creator A5077612907 @default.
• W4200329554 creator A5081334740 @default.
• W4200329554 creator A5087835347 @default.
• W4200329554 date "2021-12-01" @default.
• W4200329554 modified "2023-09-27" @default.
• W4200329554 title "How asymmetric DNA replication achieves symmetrical fidelity" @default.
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