ArticleiScience2024
TOP1 and R-loops facilitate transcriptional DSBs at hypertranscribed cancer driver genes.
Article in iScience, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- A CHK1-mediated phosphorylation switch suppresses human Topoisomerase 1-associated genomic instability.The EMBO journal · 2026Article
- Superenhancers shape the landscape and repair dynamics of transcription-associated DNA breaks in cancer.Science advances · 2026Article
- The breakome of BRCA1 and BRCA2 pathway mutation carriers reveals early processes in breast oncogenesis.Cell death & disease · 2025Article
- The interplay of DNA damage, epigenetics and tumour heterogeneity in driving cancer cell fitness.Nature communications · 2025Review
- ChromInSight: Revealing DNA Double-Strand Breaks Through Chromatin Structural Insights With an Interpretable Graph Neural Network Framework.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.Nucleic acids research · 2025Article
- Precise Mapping of Physiological DSBs Using In-Suspension Break Labeling In Situ and Sequencing (sBLISS).Methods in molecular biology (Clifton, N.J.) · 2025Article
- R-loops as a trigger for intra- and extrachromosomal DNA amplification in cancer.Frontiers in cell and developmental biology · 2025Review
- Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA double-stranded breaks (DSBs) pose a significant threat to genomic integrity, and their generation during essential cellular processes like transcription remains poorly understood. In this study, we employ several techniques to map DSBs, R-loops, and topoisomerase 1 cleavage complex (TOP1cc) to comprehensively investigate the interplay between transcription, DSBs, topoisomerase 1 (TOP1), and R-loops. Our findings reveal the presence of DSBs at highly expressed genes enriched with TOP1 and R-loops. Remarkably, transcription-associated DSBs at these loci are significantly reduced upon depletion of R-loops and TOP1, uncovering the pivotal roles of TOP1 and R-loops in transcriptional DSB formation. By elucidating the intricate interplay between TOP1cc trapping, R-loops, and DSBs, our study provides insights into the mechanisms underlying transcription-associated genomic instability. Moreover, we establish a link between transcriptional DSBs and early molecular changes driving cancer development, highlighting the distinct etiology and molecular characteristics of driver mutations compared to passenger mutations.
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