Evidence map›Paper›PMID 30060749›Full record

ArticleGenome biology2018

DNA Topoisomerase I differentially modulates R-loops across the human genome.

Stefano G Manzo, Stella R Hartono, Lionel A Sanz, Jessica Marinello, Sara De Biasi, Andrea Cossarizza, Giovanni Capranico, Frederic Chedin

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

105 citing papers in PubMed, 148 citations in OpenAlex.

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  12. Differential roles of type I topoisomerases in regulating HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
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45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Stefano G ManzoDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Stella R HartonoDepartment of Molecular and Cellular Biology and Genome Center, University of California, Davis, USA.
Lionel A SanzDepartment of Molecular and Cellular Biology and Genome Center, University of California, Davis, USA.
Jessica MarinelloDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Sara De BiasiDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
Andrea CossarizzaDepartment of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
Giovanni CapranicoDepartment of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy. giovanni.capranico@unibo.it.
Frederic ChedinDepartment of Molecular and Cellular Biology and Genome Center, University of California, Davis, USA. flchedin@ucdavis.edu.ORCID 0000-0002-1306-5335
University of California, Davis · USUniversity of Bologna · ITUniversity of Modena and Reggio Emilia · ITOncode Institute · NL

Funding

Genomic profiling of pathological R-loop formation in human diseases.R01GM120607 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CHEDIN, FREDERIC LOUIS · 2016 to 2019
$1.2M
Associazione Italiana per la Ricerca sul Cancro AIRC, IG 15886Howard Hughes Medical Institute International Student Research fellowshipNIGMS NIH HHS GM120607NIGMS NIH HHS R01 GM120607
6 · The paper itself

Abstract

backgroundCo-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.

resultsHere, 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.

conclusionsOur 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.

Indexed as

Genome, HumanTranscription, GeneticChromatin ImmunoprecipitationDNADNA ReplicationDNA Topoisomerases, Type IG1 Phase Cell Cycle CheckpointsGene SilencingHEK293 CellsHeterochromatinHistonesHumansLamin Type BNucleic Acid ConformationResting Phase, Cell CycleRNA Polymerase IIDNADNA Topoisomerases, Type IHeterochromatinHistonesLamin Type BRNA Polymerase IIRNA, Small InterferingTOP1 protein, human

Identifiers

PMID30060749
PMCPMC6066927
OpenAlexW2949842364

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.