ArticleProceedings of the National Academy of Sciences of the United States of America2011
Unique active site promotes error-free replication opposite an 8-oxo-guanine lesion by human DNA polymerase iota.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 65 citations in OpenAlex.
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- A steric gate prevents mutagenic dATP incorporation opposite 8-oxo-deoxyguanosine in mitochondrial DNA polymerases.The FEBS journal · 2025Article
- Transcription-Coupled Template Reconfiguration of 8-Oxoguanine for Error-Prone Transcription Revealed by Time-Resolved X-ray Crystallography and Molecular Dynamics.Journal of the American Chemical Society · 2025Article
- Dynamic basis for dA•dGTP and dA•d8OGTP misincorporation via Hoogsteen base pairs.Nature chemical biology · 2023Article
- Quantification and mapping of DNA modifications.RSC chemical biology · 2021Review
- Three Human Pol ι Variants with Impaired Polymerase Activity Fail to Rescue HChemical research in toxicology · 2020Article
- Estimation of the Mutagenic Potential of 8-Oxog in Nuclear Extracts of Mouse Cells Using the "Framed Mirror" Method.Methods and protocols · 2020Article
- Repair and translesion synthesis ofThe Journal of biological chemistry · 2019Article
- Location analysis of 8-oxo-7,8-dihydroguanine in DNA by polymerase-mediated differential coding.Chemical science · 2019Article
- Characterizing Watson-Crick versus Hoogsteen Base Pairing in a DNA-Protein Complex Using Nuclear Magnetic Resonance and Site-SpecificallyBiochemistry · 2019Article
- DNA polymerase ι is acetylated in response to SScientific reports · 2019Article
- "Mirror" Method to Estimate Mutagenic Activity of DNA Lesions.Methods and protocols · 2018Article
- Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism.Annual review of biochemistry · 2018Review
- Translesion DNA polymerases in eukaryotes: what makes them tick?Critical reviews in biochemistry and molecular biology · 2017Review
- Mouse DNA polymerase ι lacking the forty-two amino acids encoded by exon-2 is catalytically inactive in vitro.DNA repair · 2017Article
- A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG.The EMBO journal · 2016Article
- Structure and mechanism of error-free replication past the major benzo[a]pyrene adduct by human DNA polymerase κ.Nucleic acids research · 2016Article
- Regulation of translesion DNA synthesis: Posttranslational modification of lysine residues in key proteins.DNA repair · 2015Review
- The Werner syndrome protein limits the error-prone 8-oxo-dG lesion bypass activity of human DNA polymerase kappa.Nucleic acids research · 2014Article
- Biochemical analysis of six genetic variants of error-prone human DNA polymerase ι involved in translesion DNA synthesis.Chemical research in toxicology · 2014Article
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2 authors at 1 institution in 1 country.
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Abstract
The 8-oxo-guanine (8-oxo-G) lesion is the most abundant and mutagenic oxidative DNA damage existing in the genome. Due to its dual coding nature, 8-oxo-G causes most DNA polymerases to misincorporate adenine. Human Y-family DNA polymerase iota (polι) preferentially incorporates the correct cytosine nucleotide opposite 8-oxo-G. This unique specificity may contribute to polι's biological role in cellular protection against oxidative stress. However, the structural basis of this preferential cytosine incorporation is currently unknown. Here we present four crystal structures of polι in complex with DNA containing an 8-oxo-G lesion, paired with correct dCTP or incorrect dATP, dGTP, and dTTP nucleotides. An exceptionally narrow polι active site restricts the purine bases in a syn conformation, which prevents the dual coding properties of 8-oxo-G by inhibiting syn/anti conformational equilibrium. More importantly, the 8-oxo-G base in a syn conformation is not mutagenic in polι because its Hoogsteen edge does not form a stable base pair with dATP in the narrow active site. Instead, the syn 8-oxo-G template base forms the most stable replicating base pair with correct dCTP due to its small pyrimidine base size and enhanced hydrogen bonding with the Hoogsteen edge of 8-oxo-G. In combination with site directed mutagenesis, we show that Gln59 in the finger domain specifically interacts with the additional O(8) atom of the lesion base, which influences nucleotide selection, enzymatic efficiency, and replication stalling at the lesion site. Our work provides the structural mechanism of high-fidelity 8-oxo-G replication by a human DNA polymerase.
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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.