ArticleThe Journal of biological chemistry2012
The vital role of polymerase ζ and REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and recruitment of polymerase ζ by REV1 to replication-stalled site.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Development of Next Generation Cell-Permeable Peptide Inhibitors for the Oncological Target MAGE-A4.Journal of medicinal chemistry · 2025Article
- Cryo-EM structure of the Rev1-Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis.Nature structural & molecular biology · 2024Article
- Lead compound profiling for small molecule inhibitors of the REV1-CT/RIR Translesion synthesis Protein-Protein interaction.Bioorganic & medicinal chemistry · 2024Article
- Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment.Acta pharmaceutica Sinica. B · 2022Review
- Targeting REV7 effectively reverses 5-FU and oxaliplatin resistance in colorectal cancer.Cancer cell international · 2020Article
- Article
- Biological Evaluation of DNA Biomarkers in a Chemically Defined and Site-Specific Manner.Toxics · 2019Review
- Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature Mutagenesis in the Viral Genome.Journal of virology · 2018Article
- Mechanism of error-free replication across benzo[a]pyrene stereoisomers by Rev1 DNA polymerase.Nature communications · 2017Article
- Genomic and functional integrity of the hematopoietic system requires tolerance of oxidative DNA lesions.Blood · 2017Article
- Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction.ACS chemical biology · 2017Article
- Mutagenic Replication of NChemical research in toxicology · 2017Article
- Translesion Synthesis of 2'-Deoxyguanosine Lesions by Eukaryotic DNA Polymerases.Chemical research in toxicology · 2017Article
- Review
- Eukaryotic DNA Polymerases in Homologous Recombination.Annual review of genetics · 2016Review
- Y-family DNA polymerase-independent gap-filling translesion synthesis across aristolochic acid-derived adenine adducts in mouse cells.DNA repair · 2016Article
- Identification of the first small-molecule inhibitor of the REV7 DNA repair protein interaction.Bioorganic & medicinal chemistry · 2016Article
- A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis.Nature communications · 2016Article
- Rad18 confers hematopoietic progenitor cell DNA damage tolerance independently of the Fanconi Anemia pathway in vivo.Nucleic acids research · 2016Article
- DNA Polymerases η and ζ Combine to Bypass O(2)-[4-(3-Pyridyl)-4-oxobutyl]thymine, a DNA Adduct Formed from Tobacco Carcinogens.Chemical research in toxicology · 2016Article
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
The DNA synthesis across DNA lesions, termed translesion synthesis (TLS), is a complex process influenced by various factors. To investigate this process in mammalian cells, we examined TLS across a benzo[a]pyrene dihydrodiol epoxide-derived dG adduct (BPDE-dG) using a plasmid bearing a single BPDE-dG and genetically engineered mouse embryonic fibroblasts (MEFs). In wild-type MEFs, TLS was extremely miscoding (>90%) with G → T transversions being predominant. Knockout of the Rev1 gene decreased both the TLS efficiency and the miscoding frequency. Knockout of the Rev3L gene, coding for the catalytic subunit of pol ζ, caused even greater decreases in these two TLS parameters; almost all residual TLS were error-free. Thus, REV1 and pol ζ are critical to mutagenic, but not accurate, TLS across BPDE-dG. The introduction of human REV1 cDNA into Rev1(-/-) MEFs restored the mutagenic TLS, but a REV1 mutant lacking the C terminus did not. Yeast and mammalian three-hybrid assays revealed that the REV7 subunit of pol ζ mediated the interaction between REV3 and the REV1 C terminus. These results support the hypothesis that REV1 recruits pol ζ through the interaction with REV7. Our results also predict the existence of a minor REV1-independent pol ζ recruitment pathway. Finally, although mutagenic TLS across BPDE-dG largely depends on RAD18, experiments using Polk(-/-) Polh(-/-) Poli(-/-) triple-gene knockout MEFs unexpectedly revealed that another polymerase(s) could insert a nucleotide opposite BPDE-dG. This indicates that a non-Y family polymerase(s) can insert a nucleotide opposite BPDE-dG, but the subsequent extension from miscoding termini depends on REV1-polζ in a RAD18-dependent manner.
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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.