ArticleNucleic acids research2013
Replication of a carcinogenic nitropyrene DNA lesion by human Y-family DNA polymerase.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Establishing Linkages Among DNA Damage, Mutagenesis, and Genetic Diseases.Chemical research in toxicology · 2022Review
- 1-Nitropyrene Induced Reactive Oxygen Species-Mediated Apoptosis in Macrophages through AIF Nuclear Translocation and AMPK/Nrf-2/HO-1 Pathway Activation.Oxidative medicine and cellular longevity · 2021Article
- Error-Prone and Error-Free Translesion DNA Synthesis over Site-Specifically Created DNA Adducts of Aryl Hydrocarbons (3-Nitrobenzanthrone and 4-Aminobiphenyl).Toxicological research · 2017Review
- Identification of amino acid residues involved in the dRP-lyase activity of human Pol ι.Scientific reports · 2017Article
- Translesion Synthesis of 2'-Deoxyguanosine Lesions by Eukaryotic DNA Polymerases.Chemical research in toxicology · 2017Article
- Structure and mechanism of error-free replication past the major benzo[a]pyrene adduct by human DNA polymerase κ.Nucleic acids research · 2016Article
- Conformational Insights into the Mechanism of Acetylaminofluorene-dG-Induced Frameshift Mutations in the NarI Mutational Hotspot.Chemical research in toxicology · 2016Article
- Mechanistic Basis for the Bypass of a Bulky DNA Adduct Catalyzed by a Y-Family DNA Polymerase.Journal of the American Chemical Society · 2015Article
- Article
- An overview of Y-Family DNA polymerases and a case study of human DNA polymerase η.Biochemistry · 2014Review
- Structural mechanism of replication stalling on a bulky amino-polycyclic aromatic hydrocarbon DNA adduct by a y family DNA polymerase.Journal of molecular biology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
Nitrated polycyclic aromatic hydrocarbons are common environmental pollutants, of which many are mutagenic and carcinogenic. 1-Nitropyrene is the most abundant nitrated polycyclic aromatic hydrocarbon, which causes DNA damage and is carcinogenic in experimental animals. Error-prone translesion synthesis of 1-nitropyrene-derived DNA lesions generates mutations that likely play a role in the etiology of cancer. Here, we report two crystal structures of the human Y-family DNA polymerase iota complexed with the major 1-nitropyrene DNA lesion at the insertion stage, incorporating either dCTP or dATP nucleotide opposite the lesion. Polι maintains the adduct in its active site in two distinct conformations. dCTP forms a Watson-Crick base pair with the adducted guanine and excludes the pyrene ring from the helical DNA, which inhibits replication beyond the lesion. By contrast, the mismatched dATP stacks above the pyrene ring that is intercalated in the helix and achieves a productive conformation for misincorporation. The intra-helical bulky pyrene mimics a base pair in the active site and facilitates adenine misincorporation. By structure-based mutagenesis, we show that the restrictive active site of human polη prevents the intra-helical conformation and A-base misinsertions. This work provides one of the molecular mechanisms for G to T transversions, a signature mutation in human lung cancer.
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