ArticleNucleic acids research2014
The spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 58 citations in OpenAlex.
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- Dynamic basis for dA•dGTP and dA•d8OGTP misincorporation via Hoogsteen base pairs.Nature chemical biology · 2023Article
- Quantum Tunnelling Effects in the Guanine-Thymine Wobble Misincorporation via Tautomerism.The journal of physical chemistry letters · 2023Article
- Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair.Nature communications · 2022Article
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
- Constraints on error rate revealed by computational study of G•U tautomerization in translation.Nucleic acids research · 2021Article
- Insights into the substrate discrimination mechanisms of methyl-CpG-binding domain 4.The Biochemical journal · 2021Article
- Multiscale Modeling of Wobble to Watson-Crick-Like Guanine-Uracil Tautomerization Pathways in RNA.International journal of molecular sciences · 2021Article
- Trends of mutation accumulation across global SARS-CoV-2 genomes: Implications for the evolution of the novel coronavirus.Genomics · 2020Article
- Modulation of the Apurinic/Apyrimidinic Endonuclease Activity of Human APE1 and of Its Natural Polymorphic Variants by Base Excision Repair Proteins.International journal of molecular sciences · 2020Article
- Probing conformational transitions towards mutagenic Watson-Crick-like G·T mismatches using off-resonance sugar carbon RJournal of biomolecular NMR · 2020Article
- Environmental Effects on Guanine-Thymine Mispair Tautomerization Explored with Quantum Mechanical/Molecular Mechanical Free Energy Simulations.Journal of the American Chemical Society · 2020Article
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3 authors at 1 institution in 1 country.
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Abstract
To provide molecular-level insights into the spontaneous replication error and the mismatch discrimination mechanisms of human DNA polymerase β (polβ), we report four crystal structures of polβ complexed with dG•dTTP and dA•dCTP mismatches in the presence of Mg2+ or Mn2+. The Mg(2+)-bound ground-state structures show that the dA•dCTP-Mg2+ complex adopts an 'intermediate' protein conformation while the dG•dTTP-Mg2+ complex adopts an open protein conformation. The Mn(2+)-bound 'pre-chemistry-state' structures show that the dA•dCTP-Mn2+ complex is structurally very similar to the dA•dCTP-Mg2+ complex, whereas the dG•dTTP-Mn2+ complex undergoes a large-scale conformational change to adopt a Watson-Crick-like dG•dTTP base pair and a closed protein conformation. These structural differences, together with our molecular dynamics simulation studies, suggest that polβ increases replication fidelity via a two-stage mismatch discrimination mechanism, where one is in the ground state and the other in the closed conformation state. In the closed conformation state, polβ appears to allow only a Watson-Crick-like conformation for purine•pyrimidine base pairs, thereby discriminating the mismatched base pairs based on their ability to form the Watson-Crick-like conformation. Overall, the present studies provide new insights into the spontaneous replication error and the replication fidelity mechanisms of polβ.
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