Evidence map›Paper›PMID 32501506›Full record

ArticleNucleic acids research2020

Topoisomerase II contributes to DNA secondary structure-mediated double-stranded breaks.

Karol Szlachta, Arkadi Manukyan, Heather M Raimer, Sandeep Singh, Anita Salamon, Wenying Guo, Kirill S Lobachev, Yuh-Hwa Wang

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
  2. Article
  3. DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
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  11. Article
  12. Article
  13. Article
  14. Noval ceRNA axis-mediated high expression ofTranslational cancer research · 2023
    Article
  15. Article
  16. Article
  17. Article
  18. DNA fragility at theOpen biology · 2023
    Review
  19. The remodeling of Z-DNA in the mammalian germ line.Biochemical Society transactions · 2022
    Article
  20. Review
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 2 institutions in 1 country.

Karol SzlachtaDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908-0733, USA.
Arkadi ManukyanDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908-0733, USA.
Heather M RaimerDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908-0733, USA.
Sandeep SinghDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908-0733, USA.
Anita SalamonDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908-0733, USA.
Wenying GuoSchool of Biological Sciences and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Kirill S LobachevSchool of Biological Sciences and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Yuh-Hwa WangDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908-0733, USA.
University of Virginia · USGeorgia Institute of Technology · US

Funding

TRAINING IN CELL AND MOLECULAR BIOLOGYT32GM008136 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI STUKENBERG, P. TODD · 1985 to 2020
$8.5M
Genome-wide DNA Secondary Structure Analysis to Investigate DNA FragilityR01GM101192 · NIGMS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WANG, YUH-HWA · 2013 to 2024
$2.8M
The Role of Fragile Sites in RET/PTC RearrangementR01CA113863 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI WANG, YUH-HWA · 2006 to 2018
$2.5M
Training in Cell and Molecular BiologyT32GM139787 · NIGMS · UNIVERSITY OF VIRGINIA · PI Bryce Paschal · 2021 to 2026
$2.5M
Identification of distinct pathways for DSB formation at palindromic repeatsR01GM129119 · NIGMS · GEORGIA INSTITUTE OF TECHNOLOGY · PI LOBACHEV, KIRILL S · 2018 to 2021
$1.2M
NCI NIH HHS R01 CA113863NIGMS NIH HHS R01 GM101192NIGMS NIH HHS R01 GM129119NIGMS NIH HHS T32 GM008136NIGMS NIH HHS T32 GM139787
6 · The paper itself

Abstract

DNA double-stranded breaks (DSBs) trigger human genome instability, therefore identifying what factors contribute to DSB induction is critical for our understanding of human disease etiology. Using an unbiased, genome-wide approach, we found that genomic regions with the ability to form highly stable DNA secondary structures are enriched for endogenous DSBs in human cells. Human genomic regions predicted to form non-B-form DNA induced gross chromosomal rearrangements in yeast and displayed high indel frequency in human genomes. The extent of instability in both analyses is in concordance with the structure forming ability of these regions. We also observed an enrichment of DNA secondary structure-prone sites overlapping transcription start sites (TSSs) and CCCTC-binding factor (CTCF) binding sites, and uncovered an increase in DSBs at highly stable DNA secondary structure regions, in response to etoposide, an inhibitor of topoisomerase II (TOP2) re-ligation activity. Importantly, we found that TOP2 deficiency in both yeast and human leads to a significant reduction in DSBs at structure-prone loci, and that sites of TOP2 cleavage have a greater ability to form highly stable DNA secondary structures. This study reveals a direct role for TOP2 in generating secondary structure-mediated DNA fragility, advancing our understanding of mechanisms underlying human genome instability.

Indexed as

Binding SitesCCCTC-Binding FactorDNADNA Breaks, Double-StrandedDNA RepairDNA Topoisomerases, Type IIEtoposideGenome, HumanGenomic InstabilityHumansNucleic Acid ConformationTranscription Initiation SiteCCCTC-Binding FactorDNADNA Topoisomerases, Type IIEtoposide

Identifiers

PMID32501506
PMCPMC7337936
OpenAlexW3033871034

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

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.