ArticleThe Journal of biological chemistry2015
Error-prone translesion synthesis past DNA-peptide cross-links conjugated to the major groove of DNA via C5 of thymidine.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Engineering protein prenylation: an emerging tool for selective protein modification.Biochemical Society transactions · 2025Review
- SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.Scientific reports · 2024Article
- Monoubiquitinated H2B, a Main Chromatin Target of Formaldehyde, Is Important for S-Phase Checkpoint Signaling and Genome Stability.Molecular carcinogenesis · 2024Article
- Endogenous Cellular Metabolite Methylglyoxal Induces DNA-Protein Cross-Links in Living Cells.ACS chemical biology · 2024Article
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- Abasic site-peptide cross-links are blocking lesions repaired by AP endonucleases.Nucleic acids research · 2023Article
- Bypass of Abasic Site-Peptide Cross-Links by Human Repair and Translesion DNA Polymerases.International journal of molecular sciences · 2023Article
- Site-Specific 5-Formyl Cytosine Mediated DNA-Histone Cross-Links: Synthesis and Polymerase Bypass by Human DNA Polymerase η.Angewandte Chemie (International ed. in English) · 2021Article
- Processing and Bypass of a Site-Specific DNA Adduct of the Cytotoxic Platinum-Acridinylthiourea Conjugate by Polymerases Involved in DNA Repair: Biochemical and Thermodynamic Aspects.International journal of molecular sciences · 2021Article
- Synthesis and polymerase bypass studies of DNA-peptide and DNA-protein conjugates.Methods in enzymology · 2021Article
- How to fix DNA-protein crosslinks.DNA repair · 2020Article
- Transcriptional Bypass of DNA-Protein and DNA-Peptide Conjugates by T7 RNA Polymerase.ACS chemical biology · 2019Article
- Translesion DNA Synthesis Across Lesions Induced by Oxidative Products of Pyrimidines: An Insight into the Mechanism by Microscale Thermophoresis.International journal of molecular sciences · 2019Article
- Photodissociative Cross-Linking of Diazirine-Tagged Peptides with DNA Dinucleotides in the Gas Phase.Journal of the American Society for Mass Spectrometry · 2019Article
- Mammalian DNA Polymerase Kappa Activity and Specificity.Molecules (Basel, Switzerland) · 2019Review
- Error-prone replication of a 5-formylcytosine-mediated DNA-peptide cross-link in human cells.The Journal of biological chemistry · 2019Article
- 5-Formylcytosine mediated DNA-protein cross-links block DNA replication and induce mutations in human cells.Nucleic acids research · 2018Article
- Oxidative cross-linking of proteins to DNA following ischemia-reperfusion injury.Free radical biology & medicine · 2018Article
- Article
- Mass Spectrometry-Based Tools to Characterize DNA-Protein Cross-Linking by Bis-Electrophiles.Basic & clinical pharmacology & toxicology · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
DNA-protein cross-links (DPCs) are exceptionally bulky, structurally diverse DNA adducts formed in cells upon exposure to endogenous and exogenous bis-electrophiles, reactive oxygen species, and ionizing radiation. If not repaired, DPCs can induce toxicity and mutations. It has been proposed that the protein component of a DPC is proteolytically degraded, giving rise to smaller DNA-peptide conjugates, which can be subject to nucleotide excision repair and replication bypass. In this study, polymerase bypass of model DNA-peptide conjugates structurally analogous to the lesions induced by reactive oxygen species and DNA methyltransferase inhibitors was examined. DNA oligomers containing site-specific DNA-peptide conjugates were generated by copper-catalyzed [3 + 2] Huisgen cyclo-addition between an alkyne-functionalized C5-thymidine in DNA and an azide-containing 10-mer peptide. The resulting DNA-peptide conjugates were subjected to steady-state kinetic experiments in the presence of recombinant human lesion bypass polymerases κ and η, followed by PAGE-based assays to determine the catalytic efficiency and the misinsertion frequency opposite the lesion. We found that human polymerase κ and η can incorporate A, G, C, or T opposite the C5-dT-conjugated DNA-peptide conjugates, whereas human polymerase η preferentially inserts G opposite the lesion. Furthermore, HPLC-ESI(-)-MS/MS sequencing of the extension products has revealed that post-lesion synthesis was highly error-prone, resulting in mutations opposite the adducted site or at the +1 position from the adduct and multiple deletions. Collectively, our results indicate that replication bypass of peptides conjugated to the C5 position of thymine by human translesion synthesis polymerases leads to large numbers of base substitution and frameshift mutations.
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