ArticleThe EMBO journal2020
Excessive excision of correct nucleotides during DNA synthesis explained by replication hurdles.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- The POLγ Y951N patient mutation disrupts the switch between DNA synthesis and proofreading, triggering mitochondrial DNA instability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- DNA Polymerase Locks Replication Fork Under Stress.bioRxiv : the preprint server for biology · 2024Article
- Reclassification of family A DNA polymerases reveals novel functional subfamilies and distinctive structural features.Nucleic acids research · 2023Article
- Mechanism of strand displacement DNA synthesis by the coordinated activities of human mitochondrial DNA polymerase and SSB.Nucleic acids research · 2023Article
- Bacteriophage-Encoded DNA Polymerases-Beyond the Traditional View of Polymerase Activities.International journal of molecular sciences · 2022Review
- Quantitative methods to study helicase, DNA polymerase, and exonuclease coupling during DNA replication.Methods in enzymology · 2022Article
- Structural dynamics and determinants of 2-aminoadenine specificity in DNA polymerase DpoZ of vibriophage ϕVC8.Nucleic acids research · 2021Article
- Review
- Article
- A non-radioactive DNA synthesis assay demonstrates that elements of the Sigma 1278b Mip1 mitochondrial DNA polymerase domain and C-terminal extension facilitate robust enzyme activity.Yeast (Chichester, England) · 2021Article
- John W. (Jan) Drake: A Biochemical View of a GeneticistGenetics · 2020Article
- Excessive excision of correct nucleotides during DNA synthesis explained by replication hurdles.The EMBO journal · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The proofreading exonuclease activity of replicative DNA polymerase excises misincorporated nucleotides during DNA synthesis, but these events are rare. Therefore, we were surprised to find that T7 replisome excised nearly 7% of correctly incorporated nucleotides during leading and lagging strand syntheses. Similar observations with two other DNA polymerases establish its generality. We show that excessive excision of correctly incorporated nucleotides is not due to events such as processive degradation of nascent DNA or spontaneous partitioning of primer-end to the exonuclease site as a "cost of proofreading". Instead, we show that replication hurdles, including secondary structures in template, slowed helicase, or uncoupled helicase-polymerase, increase DNA reannealing and polymerase backtracking, and generate frayed primer-ends that are shuttled to the exonuclease site and excised efficiently. Our studies indicate that active-site shuttling occurs at a high frequency, and we propose that it serves as a proofreading mechanism to protect primer-ends from mutagenic extensions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.