ArticleThe EMBO journal2016
A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- MUTYH Cancer-Associated Variants Within the Interdomain Connector Differentially Impact Glycosylase Activity and Cellular DNA Repair.Chembiochem : a European journal of chemical biology · 2026Article
- OGG1 and MUTYH DNA Glycosylases, the Dynamic Duo Against 8-Oxoguanine DNA Lesion: Structure, Regulation, and Novel Emerging Roles.Biomolecules · 2026Review
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- DNA polymerase β suppresses somatic indels at CpG dinucleotides in developing cortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oxidative Stress and DNA Damage at Telomeres.Cold Spring Harbor perspectives in biology · 2025Review
- 5-aminolevulinic acid photodynamic therapy protects against UVB-induced skin photoaging: A DNA-repairing mechanism involving the BER signalling pathway.Journal of cellular and molecular medicine · 2024Article
- FSHing for DNA Damage: Key Features of MutY Detection of 8-Oxoguanine:Adenine Mismatches.Accounts of chemical research · 2024Review
- 8-Oxoadenine: A «New» Player of the Oxidative Stress in Mammals?International journal of molecular sciences · 2024Review
- Dynamic basis for dA•dGTP and dA•d8OGTP misincorporation via Hoogsteen base pairs.Nature chemical biology · 2023Article
- On the Role of Molecular Conformation of the 8-Oxoguanine Lesion in Damaged DNA Processing by Polymerases.Journal of chemical information and modeling · 2023Article
- Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints.Nature communications · 2022Article
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Review
- Single molecule analysis indicates stimulation of MUTYH by UV-DDB through enzyme turnover.Nucleic acids research · 2021Article
- Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.Nature communications · 2021Article
- Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.Nature communications · 2021Article
- Synthesis of 8-oxo-dGTP and its β,γ-CHTetrahedron letters · 2021Article
- DNA polymerase mu: An inflexible scaffold for substrate flexibility.DNA repair · 2020Review
- Quaternary structural diversity in eukaryotic DNA polymerases: monomeric to multimeric form.Current genetics · 2020Review
- Estimation of the Mutagenic Potential of 8-Oxog in Nuclear Extracts of Mouse Cells Using the "Framed Mirror" Method.Methods and protocols · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
8-oxo-7,8-dihydroxy-2'-deoxyguanosine (8-oxo-dG) has high mutagenic potential as it is prone to mispair with deoxyadenine (dA). In order to maintain genomic integrity, post-replicative 8-oxo-dG:dA mispairs are removed through DNA polymerase lambda (Pol λ)-dependent MUTYH-initiated base excision repair (BER). Here, we describe seven novel crystal structures and kinetic data that fully characterize 8-oxo-dG bypass by Pol λ. We demonstrate that Pol λ has a flexible active site that can tolerate 8-oxo-dG in either the anti- or syn-conformation. Importantly, we show that discrimination against the pro-mutagenic syn-conformation occurs at the extension step and identify the residue responsible for this selectivity. This residue acts as a kinetic switch, shunting repair toward long-patch BER upon correct dCMP incorporation, thus enhancing repair efficiency. Moreover, this switch also provides a potential mechanism to increase repair fidelity of MUTYH-initiated BER.
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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.