ArticleProceedings of the National Academy of Sciences of the United States of America2012
A switch between DNA polymerases δ and λ promotes error-free bypass of 8-oxo-G lesions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.Nucleic acids research · 2025Article
- Impact of an oxidative RNA lesion on in vitro replication catalyzed by SARS-CoV-2 RNA-dependent RNA polymerase.The Journal of biological chemistry · 2025Article
- Enzymatic bypass of G-quadruplex structures containing oxidative lesions.Nucleic acids research · 2025Article
- A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.bioRxiv : the preprint server for biology · 2024Article
- Aberrant Repair of 8-Oxoguanine in Short DNA Bulges.Doklady. Biochemistry and biophysics · 2023Article
- Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities.Nucleic acids research · 2022Article
- Telomeric 8-oxo-guanine drives rapid premature senescence in the absence of telomere shortening.Nature structural & molecular biology · 2022Article
- AOP report: Development of an adverse outcome pathway for oxidative DNA damage leading to mutations and chromosomal aberrations.Environmental and molecular mutagenesis · 2022Article
- Review
- Sequence context effects of replication of Fapy•dG in three mutational hot spot sequences of the p53 gene in human cells.DNA repair · 2021Article
- Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.Nature communications · 2021Article
- Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease.Frontiers in neuroscience · 2021Review
- HMCES safeguards replication from oxidative stress and ensures error-free repair.EMBO reports · 2020Article
- Estimation of the Mutagenic Potential of 8-Oxog in Nuclear Extracts of Mouse Cells Using the "Framed Mirror" Method.Methods and protocols · 2020Article
- On the epigenetic role of guanosine oxidation.Redox biology · 2020Review
- Inflammation-induced DNA damage, mutations and cancer.DNA repair · 2019Review
- Targeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis.Molecular cell · 2019Article
- Oxygen and RNA in stress-induced mutation.Current genetics · 2018Review
- Mutagenic potential of nitrogen mustard-induced formamidopyrimidine DNA adduct: Contribution of the non-canonical α-anomer.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
7,8-Dihydro-8-oxoguanine (8-oxo-G) is a highly abundant and mutagenic lesion. Replicative DNA polymerases (pols) are slowed down at 8-oxo-G and insert both correct cytosine (C) and incorrect adenine (A) opposite 8-oxo-G, but they preferentially extend A:8-oxo-G mispairs. Nevertheless, 8-oxo-G bypass is fairly accurate in vivo. Thus, the question how correct bypass of 8-oxo-G lesions is accomplished despite the poor extension of C:8-oxo-G base pairs by replicative pols remains unanswered. Here we show that replicative pol δ pauses in front of 8-oxo-G and displays difficulties extending from correct C:8-oxo-G in contrast to extension from incorrect A:8-oxo-G. This leads to stalling of pol δ at 8-oxo-G after incorporation of correct C. This stalling at C:8-oxo-G can be overcome by a switch from pol δ to pols λ, β, or η, all of which are able to assist pol δ in 8-oxo-G bypass by translesion synthesis (TLS). Importantly, however, only pol λ selectively catalyzes the correct TLS past 8-oxo-G, whereas pols β and η show no selectivity and even preferentially enhance incorrect TLS. The selectivity of pol λ to promote the correct bypass depends on its N-terminal domain. Furthermore, pol λ(-/-) mouse embryonic fibroblast extracts display reduced 8-oxo-G TLS. Finally, the correct bypass of 8-oxo-G in gapped plasmids in mouse embryonic fibroblasts and HeLa cells is promoted in the presence of pol λ. Our findings suggest that even though 8-oxo-G is not a blocking lesion per se, correct replication over 8-oxo-G is promoted by a pol switch between pols δ and λ.
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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.