ArticleProceedings of the National Academy of Sciences of the United States of America2016
RNA polymerase II senses obstruction in the DNA minor groove via a conserved sensor motif.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Stepwise transcription stalling by the anti-cancer drug Actinomycin D and insights into short tandem repeat transcription inhibition.Nature communications · 2026Article
- A cyclic pyrrole-imidazole polyamide reduces pathogenic RNA in CAG/CTG triplet repeat neurological disease models.The Journal of clinical investigation · 2023Article
- RNA polymerase II trapped on a molecular treadmill: Structural basis of persistent transcriptional arrest by a minor groove DNA binder.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Polymerases and DNA Repair in Neurons: Implications in Neuronal Survival and Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Opposite roles of transcription elongation factors Spt4/5 and Elf1 in RNA polymerase II transcription through B-form versus non-B DNA structures.Nucleic acids research · 2021Article
- Natural and Synthetic Oligoarylamides: Privileged Structures for Medical Applications.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Review
- Molecular basis of transcriptional pausing, stalling, and transcription-coupled repair initiation.Biochimica et biophysica acta. Gene regulatory mechanisms · 2021Review
- Formation and Recognition of UV-Induced DNA Damage within Genome Complexity.International journal of molecular sciences · 2020Review
- Role of the trigger loop in translesion RNA synthesis by bacterial RNA polymerase.The Journal of biological chemistry · 2020Article
- The Road Not Taken with Pyrrole-Imidazole Polyamides: Off-Target Effects and Genomic Binding.Biomolecules · 2020Review
- Single position substitution of hairpin pyrrole-imidazole polyamides imparts distinct DNA-binding profiles across the human genome.PloS one · 2020Article
- Structural and biochemical analysis of DNA lesion-induced RNA polymerase II arrest.Methods (San Diego, Calif.) · 2019Review
- Structural basis of DNA lesion recognition for eukaryotic transcription-coupled nucleotide excision repair.DNA repair · 2018Review
- Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides.Nucleic acids research · 2018Article
- Interference with DNA repair after ionizing radiation by a pyrrole-imidazole polyamide.PloS one · 2018Article
- Article
- Mechanism of RNA polymerase II stalling by DNA alkylation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Mechanism of DNA alkylation-induced transcriptional stalling, lesion bypass, and mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A Pyrrole-Imidazole Polyamide Is Active against Enzalutamide-Resistant Prostate Cancer.Cancer research · 2017Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
RNA polymerase II (pol II) encounters numerous barriers during transcription elongation, including DNA strand breaks, DNA lesions, and nucleosomes. Pyrrole-imidazole (Py-Im) polyamides bind to the minor groove of DNA with programmable sequence specificity and high affinity. Previous studies suggest that Py-Im polyamides can prevent transcription factor binding, as well as interfere with pol II transcription elongation. However, the mechanism of pol II inhibition by Py-Im polyamides is unclear. Here we investigate the mechanism of how these minor-groove binders affect pol II transcription elongation. In the presence of site-specifically bound Py-Im polyamides, we find that the pol II elongation complex becomes arrested immediately upstream of the targeted DNA sequence, and is not rescued by transcription factor IIS, which is in contrast to pol II blockage by a nucleosome barrier. Further analysis reveals that two conserved pol II residues in the Switch 1 region contribute to pol II stalling. Our study suggests this motif in pol II can sense the structural changes of the DNA minor groove and can be considered a "minor groove sensor." Prolonged interference of transcription elongation by sequence-specific minor groove binders may present opportunities to target transcription addiction for cancer therapy.
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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.