ArticlePloS one2016
Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters.
Article in PloS one, 2016. 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, 54 citations in OpenAlex.
- RNA damage and its implications in genome stability.DNA repair · 2025Review
- Looping forward: exploring R-loop processing and therapeutic potential.FEBS letters · 2025Review
- The hidden architects of the genome: a comprehensive review of R-loops.Molecular biology reports · 2024Review
- Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS.Science advances · 2024Article
- Topoisomerase 1 Inhibition in MYC-Driven Cancer Promotes Aberrant R-Loop Accumulation to Induce Synthetic Lethality.Cancer research · 2023Article
- TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.Nature communications · 2023Article
- NUSAP1 Binds ILF2 to Modulate R-Loop Accumulation and DNA Damage in Prostate Cancer.International journal of molecular sciences · 2023Article
- Resolution of R-loops by topoisomerase III-β (TOP3B) in coordination with the DEAD-box helicase DDX5.Cell reports · 2022Article
- Transcription-Replication Coordination.Life (Basel, Switzerland) · 2022Review
- Review
- Functions of the CSB Protein at Topoisomerase 2 Inhibitors-Induced DNA Lesions.Frontiers in cell and developmental biology · 2021Article
- A Tale of Loops and Tails: The Role of Intrinsically Disordered Protein Regions in R-Loop Recognition and Phase Separation.Frontiers in molecular biosciences · 2021Article
- G-quadruplex-R-loop interactions and the mechanism of anticancer G-quadruplex binders.Nucleic acids research · 2020Review
- PARylation During Transcription: Insights into the Fine-Tuning Mechanism and Regulation.Cancers · 2020Review
- The DNA secondary structures at telomeres and genome instability.Cell & bioscience · 2020Review
- Dual Processing of R-Loops and Topoisomerase I Induces Transcription-Dependent DNA Double-Strand Breaks.Cell reports · 2019Article
- Chemotherapeutic Drugs Inhibiting Topoisomerase 1 Activity Impede Cytokine-Induced and NF-κB p65-Regulated Gene Expression.Cancers · 2019Article
- Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- DNA Topoisomerase I differentially modulates R-loops across the human genome.Genome biology · 2018Article
- RNA/DNA Hybrid Interactome Identifies DXH9 as a Molecular Player in Transcriptional Termination and R-Loop-Associated DNA Damage.Cell reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Topoisomerase I-DNA-cleavage complexes (Top1cc) stabilized by camptothecin (CPT) have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs) levels at divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop) in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops and aRNAs was not established. Here, we show that aRNAs can form R-loops in N-TERA-2 cells under physiological conditions, and that promoter-associated R-loops are somewhat increased and extended in length immediately upon cell exposure to CPT. In contrast, persistent Top1ccs reduce the majority of R-loops suggesting that CPT-accumulated aRNAs are not commonly involved in R-loops. The enhancement of aRNAs by Top1ccs is present both in human colon cancer HCT116 cells and WI38 fibroblasts suggesting a common response of cancer and normal cells. Although Top1ccs lead to DSB and DDR kinases activation, we do not detect a dependence of aRNA accumulation on ATM or DNA-PK activation. However, we showed that the cell response to persistent Top1ccs can involve an impairment of aRNA turnover rather than a higher synthesis rate. Finally, a genome-wide analysis shows that persistent Top1ccs also determine an accumulation of sense transcripts at 5'-end gene regions suggesting an increased occurrence of truncated transcripts. Taken together, the results indicate that Top1 may regulate transcription initiation by modulating RNA polymerase-generated negative supercoils, which can in turn favor R-loop formation at promoters, and that transcript accumulation at TSS is a response to persistent transcriptional stress by Top1 poisoning.
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Registered trials
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.