Evidence map›Paper›PMID 40764613›Full record

ArticleNature communications2025

Substrate accessibility regulation of human TopIIa decatenation by cohesin.

Erin E Cutts, Sanjana Saravanan, Paul Girvan, Benjamin Ambrose, Gemma L M Fisher, David S Rueda, Luis Aragon

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. 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.

Erin E CuttsDNA Motors Group, MRC Laboratory of Medical Sciences, Du Cane Road, London, W12 0HS, UK.ORCID http://orcid.org/0000-0003-3290-4293
Sanjana SaravananDNA Motors Group, MRC Laboratory of Medical Sciences, Du Cane Road, London, W12 0HS, UK.ORCID http://orcid.org/0000-0002-5974-7710
Paul GirvanSingle Molecule Imaging Group, MRC Laboratory of Medical Sciences, Du Cane Road, London, W12 0HS, UK.ORCID http://orcid.org/0000-0003-1411-0094
Benjamin AmbroseSingle Molecule Imaging Group, MRC Laboratory of Medical Sciences, Du Cane Road, London, W12 0HS, UK.
Gemma L M FisherDNA Motors Group, MRC Laboratory of Medical Sciences, Du Cane Road, London, W12 0HS, UK.ORCID http://orcid.org/0000-0001-8468-5032
David S RuedaSingle Molecule Imaging Group, MRC Laboratory of Medical Sciences, Du Cane Road, London, W12 0HS, UK. david.rueda@imperial.ac.uk.ORCID http://orcid.org/0000-0003-4657-6323
Luis AragonDNA Motors Group, MRC Laboratory of Medical Sciences, Du Cane Road, London, W12 0HS, UK. luis.aragon@lms.mrc.ac.uk.ORCID http://orcid.org/0000-0003-0634-6742

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human topoisomerase II alpha (TOP2α) resolves DNA intertwines between sister chromatids during mitosis. How cohesin, an SMC complex that holds sister chromatids, affects TOP2α decatenation is unclear. To addres this, we developed a quadruple-trap optical tweezers assay to create DNA braids and study TOP2α decatenation at the single-molecule level in real-time. We show that TOP2α resolves both single and multiple braids but becomes inefficient at forces exceeding 28 pN. TOP2α is sensitive to DNA geometry, exhibiting a chiral preference for right-handed braid crossings, and requires loading directly at DNA crossovers to act. Pre-loading TOP2α onto individual DNA strands before braid formation, in the presence of ATP, prevents decatenation. Finally, we show that human cohesin, but not condensin I, binds stably to DNA braids and blocks TOP2α activity. Our study provides novel insights into the role of substrate accessibility in regulating TOP2α's activity and highlights cohesin as a barrier to decatenation.

Indexed as

Cell Cycle ProteinsChromosomal Proteins, Non-HistoneDNA, CatenatedDNA Topoisomerases, Type IIPoly-ADP-Ribose Binding ProteinsAdenosine TriphosphatasesChromatidsCohesinsDNADNA-Binding ProteinsHumansMultiprotein ComplexesProtein BindingAdenosine TriphosphatasesCell Cycle ProteinsChromosomal Proteins, Non-HistoneCohesinscondensin complexesDNADNA-Binding ProteinsDNA, CatenatedDNA Topoisomerases, Type IIMultiprotein ComplexesPoly-ADP-Ribose Binding ProteinsTOP2A protein, human

Identifiers

PMID40764613
PMCPMC12326010

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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.