ArticleThe Biochemical journal2020
Translesion synthesis of the major nitrogen mustard-induced DNA lesion by human DNA polymerase η.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Synthesis and Characterization of Chemically Stable N7-dG Estrone and Catechol Adducts.Molecules (Basel, Switzerland) · 2026Article
- Deciphering the Role of DNA Polymerase Eta on the Incorporation and Bypass of Inosine and Cell Cycle Arrest.International journal of molecular sciences · 2025Article
- Current progress in research on ocular injury caused by exposure to vesicants.Progress in retinal and eye research · 2025Review
- Peptide Sequence and Cross-Link Structure Influence Translesion Synthesis Polymerase Bypass of 5-Formylcytosine-Mediated DNA-Peptide Cross-Links.Chemical research in toxicology · 2025Article
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- Structural Insights into the Nonmutagenicity of 2-Haloacetophenone.Molecules (Basel, Switzerland) · 2025Article
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer.Bioscience reports · 2024Review
- Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer.Nucleic acids research · 2024Article
- Repair and tolerance of DNA damage at the replication fork: A structural perspective.Current opinion in structural biology · 2023Review
- Genotoxic effects of the major alkylation damage N7-methylguanine and methyl formamidopyrimidine.The Biochemical journal · 2023Article
- Translesion Synthesis Past 5-Formylcytosine-Mediated DNA-Peptide Cross-Links by hPolη Is Dependent on the Local DNA Sequence.Biochemistry · 2021Article
- Beyond the Lesion: Back to High Fidelity DNA Synthesis.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Nitrogen mustards are among the first modern anticancer chemotherapeutics that are still widely used as non-specific anticancer alkylating agents. While the mechanism of action of mustard drugs involves the generation of DNA interstrand cross-links, the predominant lesions produced by these drugs are nitrogen half-mustard-N7-dG (NHMG) adducts. The bulky major groove lesion NHMG, if left unrepaired, can be bypassed by translesion synthesis (TLS) DNA polymerases. However, studies of the TLS past NHMG have not been reported so far. Here, we present the first synthesis of an oligonucleotide containing a site-specific NHMG. We also report kinetic and structural characterization of human DNA polymerase η (polη) bypassing NHMG. The templating NHMG slows dCTP incorporation ∼130-fold, while it increases the misincorporation frequency ∼10-30-fold, highlighting the promutagenic nature of NHMG. A crystal structure of polη incorporating dCTP opposite NHMG shows a Watson-Crick NHMG:dCTP base pair with a large propeller twist angle. The nitrogen half-mustard moiety fits snugly into an open cleft created by the Arg61-Trp64 loop of polη, suggesting a role of the Arg61-Trp64 loop in accommodating bulky major groove adducts during lesion bypass. Overall, our results presented here to provide first insights into the TLS of the major DNA adduct formed by nitrogen mustard drugs.
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Registered trials
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