Evidence map›Paper›PMID 36717711›Full record

ArticleNature chemical biology2023

Etoposide promotes DNA loop trapping and barrier formation by topoisomerase II.

Tung T Le, Meiling Wu, Joyce H Lee, Neti Bhatt, James T Inman, James M Berger, Michelle D Wang

Open access · hybridAbstract read
In one paragraph

Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
9.4field-weighted citation impact, top 1% 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

47 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

7 authors at 3 institutions in 1 country.

Tung T Le *Howard Hughes Medical Institute, Cornell University, Ithaca, NY, USA.
Meiling Wu *Howard Hughes Medical Institute, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-8827-2999
Joyce H LeeDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neti BhattDepartment of Physics and LASSP, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0002-7374-2537
James T InmanHoward Hughes Medical Institute, Cornell University, Ithaca, NY, USA.
James M BergerDepartment of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-0666-1240
Michelle D WangHoward Hughes Medical Institute, Cornell University, Ithaca, NY, USA. mwang@physics.cornell.edu.ORCID http://orcid.org/0000-0001-9137-3790
Howard Hughes Medical Institute · USJohns Hopkins University · USCornell University · US

Funding

TRAINING IN MOLECULAR PHYSICS OF BIOLOGICAL SYSTEMST32GM008267 · NIGMS · CORNELL UNIVERSITY ITHACA · PI WANG, MICHELLE D. · 1988 to 2021
$9.6M
Structural and Biochemical Analyses of Type II DNA TopoisomerasesR01CA077373 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI BERGER, JAMES M. · 1999 to 2021
$7.6M
Understanding and exploiting DNA topoisomerases in cancer biologyR35CA263778 · NCI · JOHNS HOPKINS UNIVERSITY · PI James M. Berger · 2021 to 2026
$5.0M
Fundamental Biological Processes Under TorsionR01GM136894 · NIGMS · CORNELL UNIVERSITY · PI WANG, MICHELLE D. · 2020 to 2023
$1.2M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA077373NCI NIH HHS R35 CA263778NIGMS NIH HHS R01 GM136894NIGMS NIH HHS T32 GM008267
6 · The paper itself

Abstract

Etoposide is a broadly employed chemotherapeutic and eukaryotic topoisomerase II poison that stabilizes cleaved DNA intermediates to promote DNA breakage and cytotoxicity. How etoposide perturbs topoisomerase dynamics is not known. Here we investigated the action of etoposide on yeast topoisomerase II, human topoisomerase IIα and human topoisomerase IIβ using several sensitive single-molecule detection methods. Unexpectedly, we found that etoposide induces topoisomerase to trap DNA loops, compacting DNA and restructuring DNA topology. Loop trapping occurs after ATP hydrolysis but before strand ejection from the enzyme. Although etoposide decreases the innate stability of topoisomerase dimers, it increases the ability of the enzyme to act as a stable roadblock. Interestingly, the three topoisomerases show similar etoposide-mediated resistance to dimer separation and sliding along DNA but different abilities to compact DNA and chirally relax DNA supercoils. These data provide unique mechanistic insights into the functional consequences of etoposide on topoisomerase II dynamics.

Indexed as

DNA Topoisomerases, Type IITopoisomerase II InhibitorsDNAEtoposideHumansDNADNA Topoisomerases, Type IIEtoposideTopoisomerase II Inhibitors

Identifiers

PMID36717711
PMCPMC10154222
OpenAlexW4318486666

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.