ArticleNucleic acids research2018
I260Q DNA polymerase β highlights precatalytic conformational rearrangements critical for fidelity.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- Conformational gating governs nucleotide incorporation by a DNA-crosslinked polymerase.Nucleic acids research · 2026Article
- The S180R Human Germline Variant of DNA Polymerase β Is a Low Fidelity Enzyme with Reduced Flexibility of the Fingers Domain.Biochemistry · 2026Article
- Article
- Modifying the Basicity of the dNTP Leaving Group Modulates Precatalytic Conformational Changes of DNA Polymerase β.Biochemistry · 2024Article
- Unfilled gaps by polβ lead to aberrant ligation by LIG1 at the downstream steps of base excision repair pathway.Nucleic acids research · 2024Article
- The Impact of SNP-Induced Amino Acid Substitutions L19P and G66R in the dRP-Lyase Domain of Human DNA Polymerase β on Enzyme Activities.International journal of molecular sciences · 2024Article
- Covalent PARylation of DNA base excision repair proteins regulates DNA demethylation.Nature communications · 2024Article
- Polβ/XRCC1 heterodimerization dictates DNA damage recognition and basal Polβ protein levels without interfering with mouse viability or fertility.DNA repair · 2023Article
- Analysis of coordinated NMR chemical shifts to map allosteric regulatory networks in proteins.Methods (San Diego, Calif.) · 2023Article
- The importance of residue-level filtering and the Top2018 best-parts dataset of high-quality protein residues.Protein science : a publication of the Protein Society · 2022Article
- Article
- Using single-molecule FRET to probe the nucleotide-dependent conformational landscape of polymerase β-DNA complexes.The Journal of biological chemistry · 2020Article
- NMR and computational methods for molecular resolution of allosteric pathways in enzyme complexes.Biophysical reviews · 2020Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
DNA polymerase β (pol β) fills single nucleotide gaps in DNA during base excision repair and non-homologous end-joining. Pol β must select the correct nucleotide from among a pool of four nucleotides with similar structures and properties in order to maintain genomic stability during DNA repair. Here, we use a combination of X-ray crystallography, fluorescence resonance energy transfer and nuclear magnetic resonance to show that pol β's ability to access the appropriate conformations both before and upon binding to nucleotide substrates is integral to its fidelity. Importantly, we also demonstrate that the inability of the I260Q mutator variant of pol β to properly navigate this conformational landscape results in error-prone DNA synthesis. Our work reveals that precatalytic conformational rearrangements themselves are an important underlying mechanism of substrate selection by DNA pol β.
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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.