ArticleProceedings of the National Academy of Sciences of the United States of America2020
RNA polymerase II stalls on oxidative DNA damage via a torsion-latch mechanism involving lone pair-π and CH-π interactions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. 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, 40 citations in OpenAlex.
- Communication is key: combinatorial phosphorylation and functional cross-talk in the RNA polymerase II CTD code.Biochemical Society transactions · 2026Review
- Navigating the base excision repair pathway in chromatin-focus on oxidative DNA damage.Nucleic acids research · 2026Review
- Oxidative stress triggers RNAPII arrest through PARylation and DNA damage.Nature communications · 2026Article
- Click-code-seq reveals strand biases of DNA oxidation and depurination in human genome.Nature chemical biology · 2026Article
- Structural basis of transcription-coupled RNA damage by incorporation of oxidized ribonucleotides.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanisms of transcription-coupled repair and DNA damage surveillance in health and disease.Nature reviews. Molecular cell biology · 2026Review
- Dynamic genome-wide mapping reveals how chromatin context shapes OGG1-mediated repair and related mutagenesis in human cells.Nucleic acids research · 2025Article
- Transcription-Coupled Nucleotide Excision Repair: A Faster Solution or the Only Option?Biomolecules · 2025Review
- Transcription-Coupled Template Reconfiguration of 8-Oxoguanine for Error-Prone Transcription Revealed by Time-Resolved X-ray Crystallography and Molecular Dynamics.Journal of the American Chemical Society · 2025Article
- Keep calm and reboot - how cells restart transcription after DNA damage and DNA repair.FEBS letters · 2025Review
- Promoter dependent RNA polymerase II bypass of the epimerizable DNA lesion, Fapy•dG and 8-Oxo-2'-deoxyguanosine.Nucleic acids research · 2024Article
- Molecular Mechanism of RNA Polymerase II Transcriptional Mutagenesis by the Epimerizable DNA Lesion, Fapy·dG.Journal of the American Chemical Society · 2024Article
- A unified Watson-Crick geometry drives transcription of six-letter expanded DNA alphabets by E. coli RNA polymerase.Nature communications · 2023Article
- Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.International journal of molecular sciences · 2023Review
- Developmental Stage-Dependent Changes in Mitochondrial Function in the Brain of Offspring Following Prenatal Maternal Immune Activation.International journal of molecular sciences · 2023Article
- Nanopore sequencing for N1-methylpseudouridine in RNA reveals sequence-dependent discrimination of the modified nucleotide triphosphate during transcription.Nucleic acids research · 2023Article
- 8-Oxoguanine Forms Quartets with a Large Central Cavity.Biochemistry · 2022Article
- Structural insights into the dual activities of the two-barrel RNA polymerase QDE-1.Nucleic acids research · 2022Article
- Transcriptional Perturbations of 2,6-Diaminopurine and 2-Aminopurine.ACS chemical biology · 2022Article
- RNA polymerase pausing, stalling and bypass during transcription of damaged DNA: from molecular basis to functional consequences.Nucleic acids research · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidation of guanine generates several types of DNA lesions, such as 8-oxoguanine (8OG), 5-guanidinohydantoin (Gh), and spiroiminodihydantoin (Sp). These guanine-derived oxidative DNA lesions interfere with both replication and transcription. However, the molecular mechanism of transcription processing of Gh and Sp remains unknown. In this study, by combining biochemical and structural analysis, we revealed distinct transcriptional processing of these chemically related oxidized lesions: 8OG allows both error-free and error-prone bypass, whereas Gh or Sp causes strong stalling and only allows slow error-prone incorporation of purines. Our structural studies provide snapshots of how polymerase II (Pol II) is stalled by a nonbulky Gh lesion in a stepwise manner, including the initial lesion encounter, ATP binding, ATP incorporation, jammed translocation, and arrested states. We show that while Gh can form hydrogen bonds with adenosine monophosphate (AMP) during incorporation, this base pair hydrogen bonding is not sufficient to hold an ATP substrate in the addition site and is not stable during Pol II translocation after the chemistry step. Intriguingly, we reveal a unique structural reconfiguration of the Gh lesion in which the hydantoin ring rotates ∼90° and is perpendicular to the upstream base pair planes. The perpendicular hydantoin ring of Gh is stabilized by noncanonical lone pair-π and CH-π interactions, as well as hydrogen bonds. As a result, the Gh lesion, as a functional mimic of a 1,2-intrastrand crosslink, occupies canonical -1 and +1 template positions and compromises the loading of the downstream template base. Furthermore, we suggest Gh and Sp lesions are potential targets of transcription-coupled repair.
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