ArticleProceedings of the National Academy of Sciences of the United States of America2017
Mechanism of RNA polymerase II stalling by DNA alkylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Click-code-seq reveals strand biases of DNA oxidation and depurination in human genome.Nature chemical biology · 2026Article
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- The Pathogenic Role of the DNA Double-Stranded Breaks in Hereditary Cardiomyopathies.Heart failure clinics · 2026Review
- Transcription-Coupled Nucleotide Excision Repair: A Faster Solution or the Only Option?Biomolecules · 2025Review
- Causes and consequences of DNA double-stranded breaks in cardiovascular disease.Molecular and cellular biochemistry · 2025Review
- RNA damage and its implications in genome stability.DNA repair · 2025Review
- Catalytic and noncatalytic functions of DNA polymerase κ in translesion DNA synthesis.Nature structural & molecular biology · 2025Article
- Deaminase-Driven Reverse Transcription Mutagenesis in Oncogenesis: Critical Analysis of Transcriptional Strand Asymmetries of Single Base Substitution Signatures.International journal of molecular sciences · 2025Review
- RFWD3 and translesion DNA polymerases contribute to PCNA modification-dependent DNA damage tolerance.Life science alliance · 2022Article
- RNA polymerase pausing, stalling and bypass during transcription of damaged DNA: from molecular basis to functional consequences.Nucleic acids research · 2022Review
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- The complexity and regulation of repair of alkylation damage to nucleic acids.Critical reviews in biochemistry and molecular biology · 2021Review
- Molecular basis of transcriptional pausing, stalling, and transcription-coupled repair initiation.Biochimica et biophysica acta. Gene regulatory mechanisms · 2021Review
- Alkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression.Nature communications · 2019Article
- How do cells cope with RNA damage and its consequences?The Journal of biological chemistry · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several anticancer agents that form DNA adducts in the minor groove interfere with DNA replication and transcription to induce apoptosis. Therapeutic resistance can occur, however, when cells are proficient in the removal of drug-induced damage. Acylfulvenes are a class of experimental anticancer agents with a unique repair profile suggesting their capacity to stall RNA polymerase (Pol) II and trigger transcription-coupled nucleotide excision repair. Here we show how different forms of DNA alkylation impair transcription by RNA Pol II in cells and with the isolated enzyme and unravel a mode of RNA Pol II stalling that is due to alkylation of DNA in the minor groove. We incorporated a model for acylfulvene adducts, the stable 3-deaza-3-methoxynaphtylethyl-adenosine analog (3d-Napht-A), and smaller 3-deaza-adenosine analogs, into DNA oligonucleotides to assess RNA Pol II transcription elongation in vitro. RNA Pol II was strongly blocked by a 3d-Napht-A analog but bypassed smaller analogs. Crystal structure analysis revealed that a DNA base containing 3d-Napht-A can occupy the +1 templating position and impair closing of the trigger loop in the Pol II active center and polymerase translocation into the next template position. These results show how RNA Pol II copes with minor-groove DNA alkylation and establishes a mechanism for drug resistance.
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