ArticleProceedings of the National Academy of Sciences of the United States of America2020
DNA polymerase δ proofreads errors made by DNA polymerase ε.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Response of the replisome to araA and araC suggests a mechanism for arabinosyl nucleoside tolerance.The EMBO journal · 2026Article
- APOBEC3 activity and DNA polymerase-ε deficiency are associated with distinct IDH1 R132 hotspot mutations.Molecular oncology · 2026Article
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- Traditional and New Views on MSI-H/dMMR Endometrial Cancer.Biomolecules · 2025Review
- Evidence that DNA polymerase δ proofreads errors made by DNA polymerase α across the Saccharomyces cerevisiae nuclear genome.DNA repair · 2024Article
- POLD4 Promotes Glioma Cell Proliferation and Suppressive Immune Microenvironment: A Pan-Cancer Analysis Integrated with Experimental Validation.International journal of molecular sciences · 2023Article
- Article
- Extrinsic proofreading.DNA repair · 2022Review
- Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.Annual review of biochemistry · 2022Review
- Post-Translational Modifications of PCNA: Guiding for the Best DNA Damage Tolerance Choice.Journal of fungi (Basel, Switzerland) · 2022Review
- Review
- How asymmetric DNA replication achieves symmetrical fidelity.Nature structural & molecular biology · 2021Article
- Compensation for the absence of the catalytically active half of DNA polymerase ε in yeast by positively selected mutations in CDC28.Genetics · 2021Article
- Mutagenic mechanisms of cancer-associated DNA polymerase ϵ alleles.Nucleic acids research · 2021Article
- Mechanisms for Maintaining Eukaryotic Replisome Progression in the Presence of DNA Damage.Frontiers in molecular biosciences · 2021Review
- Increased expression of Polδ does not alter the canonical replication programWellcome open research · 2021Article
- DNA Polymerases at the Eukaryotic Replication Fork Thirty Years after: Connection to Cancer.Cancers · 2020Review
- Mismatch repair and DNA polymerase δ proofreading prevent catastrophic accumulation of leading strand errors in cells expressing a cancer-associated DNA polymerase ϵ variant.Nucleic acids research · 2020Article
- Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
During eukaryotic replication, DNA polymerases ε (Polε) and δ (Polδ) synthesize the leading and lagging strands, respectively. In a long-known contradiction to this model, defects in the fidelity of Polε have a much weaker impact on mutagenesis than analogous Polδ defects. It has been previously proposed that Polδ contributes more to mutation avoidance because it proofreads mismatches created by Polε 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 Polε nucleotide selectivity defect is combined with a Polδ proofreading defect, demonstrating extrinsic proofreading of Polε errors by Polδ. In contrast, combining Polδ nucleotide selectivity and Polε proofreading defects produces no synergy, indicating that Polε cannot correct errors made by Polδ. We further show that Polδ can remove errors made by exonuclease-deficient Polε in vitro. These findings illustrate the complexity of the one-strand-one-polymerase model where synthesis appears to be largely divided, but Polδ proofreading operates on both strands.
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Registered trials
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