Faculty Opinions recommendation of DNA Topoisomerase I differentially modulates R-loops across the human genome.
Year: 2019
Type: peer-review
Abstract: Background: 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.Results: 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.Conclusions: 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.
Author: Scott Kaufmann
Institution: Mayo Clinic
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4255375224