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- W2949842364 abstract "Co-transcriptional R-loops are abundant non-B DNA structures in mammalian genomes. DNA Topoisomerase I (Top1) is often thought to regulate R-loop formation owing to its ability to resolve both positive and negative supercoils. How Top1 regulates R-loop structures at a global level is unknown. Here, we perform high-resolution strand-specific R-loop mapping in human cells depleted for Top1 and find that Top1 depletion results in both R-loop gains and losses at thousands of transcribed loci, delineating two distinct gene classes. R-loop gains are characteristic for long, highly transcribed, genes located in gene-poor regions anchored to Lamin B1 domains and in proximity to H3K9me3-marked heterochromatic patches. R-loop losses, by contrast, occur in gene-rich regions overlapping H3K27me3-marked active replication initiation regions. Interestingly, Top1 depletion coincides with a block of the cell cycle in G0/G1 phase and a trend towards replication delay. Our findings reveal new properties of Top1 in regulating R-loop homeostasis in a context-dependent manner and suggest a potential role for Top1 in modulating the replication process via R-loop formation." @default.
- W2949842364 created "2019-06-27" @default.
- W2949842364 creator A5018307013 @default.
- W2949842364 creator A5021210092 @default.
- W2949842364 creator A5023122991 @default.
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- W2949842364 creator A5083273366 @default.
- W2949842364 creator A5083279701 @default.
- W2949842364 creator A5089156584 @default.
- W2949842364 date "2018-07-30" @default.
- W2949842364 modified "2023-10-06" @default.
- W2949842364 title "DNA Topoisomerase I differentially modulates R-loops across the human genome" @default.
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- W2949842364 doi "https://doi.org/10.1186/s13059-018-1478-1" @default.
- W2949842364 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6066927" @default.
- W2949842364 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30060749" @default.
- W2949842364 hasPublicationYear "2018" @default.
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