ArticleNature communications2023
Structural basis for DNA proofreading.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Molecular and structural basis for replication initiation and strand separation by human mitochondrial DNA polymerase γ.Nucleic acids research · 2026Article
- Structural and single-molecule insights into the core human mitochondrial DNA replisome.The Biochemical journal · 2026Review
- Atomistic Simulations Decode the Mechanisms of DNA and RNA Processing Enzymes: Function through Motion.Accounts of chemical research · 2026Article
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Nature communications · 2026Article
- Coordinated transfer of DNA between Pol θ and Pol δ resets microhomology choice during double-strand break repair.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Assessing the contribution of rare DNA states to cancer mutational signatures using sequence-specific conformational fingerprinting.Research square · 2025Article
- The proofreading mechanism of the human leading-strand DNA polymerase ε holoenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease.Nature communications · 2025Article
- 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
- Structural basis for intrinsic strand displacement activity of mitochondrial DNA polymerase.Nature communications · 2025Article
- Cryo-EM Structures of the Plasmodium falciparum Apicoplast DNA Polymerase.Journal of molecular biology · 2024Article
- Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε.Nature structural & molecular biology · 2024Article
- Advances in Immunotherapy for Endometrial Cancer: Insights into MMR Status and Tumor Microenvironment.Cancers · 2024Review
- Coordinated DNA polymerization by Polγ and the region of LonP1 regulated proteolysis.Nucleic acids research · 2024Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement of the mismatched base into the exonuclease site. Altogether, our findings suggest a conserved 'bolt-action' mechanism of proofreading based on iterative cycles of DNAP translocation without dissociation from the DNA, facilitating primer transfer between catalytic sites. Functional assays and mutagenesis corroborate this mechanism, connecting pathogenic mutations to crucial structural elements in proofreading steps.
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