Evidence mapPaperPMID 41663397Full record

ArticleNature communications2026

MYC modulates TOP2A diffusion to promote substrate detection and activity.

Donald P Cameron, Kathryn Jackson, Alessia Loffreda, Carl Möller, Vladislav Kuzin, Matteo Mazzocca, Evanthia Iliopoulou, Hallgerdur Kolbeinsdottir, Andrej Paluda, Evgeniya Pavlova and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

16 authors.

Donald P Cameron *Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3175-6965
Kathryn Jackson *Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Alessia LoffredaExperimental Imaging Center, IRCCS Ospedale San Raffaele, Milano, Italy.ORCID 0000-0003-4523-5666
Carl MöllerDepartment of Life Sciences, Chalmers University of Technology, Göteborg, Sweden.ORCID 0000-0001-9463-6402
Vladislav KuzinDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Matteo MazzoccaExperimental Imaging Center, IRCCS Ospedale San Raffaele, Milano, Italy.ORCID 0000-0003-2079-1535
Evanthia IliopoulouDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Hallgerdur KolbeinsdottirDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Andrej PaludaInstitute for Quantitative Biosciences, University of Tokyo, Tokyo, Japan.ORCID 0000-0002-0716-0512
Evgeniya PavlovaDepartment of Life Sciences, Chalmers University of Technology, Göteborg, Sweden.
Bea JagodicDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.ORCID 0009-0005-0997-8130
Brian Saidel Lopez DuranUniversité de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Strasbourg, France.
Valérie LamourUniversité de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Strasbourg, France.ORCID 0000-0001-7793-4029
Fredrik WesterlundDepartment of Life Sciences, Chalmers University of Technology, Göteborg, Sweden.ORCID 0000-0002-4767-4868
Davide MazzaExperimental Imaging Center, IRCCS Ospedale San Raffaele, Milano, Italy. mazza.davide@unisr.it.ORCID 0000-0003-2776-4142
Laura BaranelloDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. laura.baranello@ki.se.ORCID 0000-0001-6039-1849

Funding

ERC ConsolidatorWorldwide Cancer Research
6 · The paper itself

Abstract

Topoisomerases alleviate DNA supercoiling by cleaving and resealing DNA strands. Previously, we showed that the oncoprotein MYC recruits and stimulates topoisomerases to remove DNA entanglements generated by oncogenic transcription. Understanding this mechanism may suggest methods to inhibit MYC-driven topoisomerase activation, targeting tumor-specific transcription. Here, we demonstrate that the essential topoisomerase TOP2A in human cells exists in a dynamic equilibrium between sequestration in the nucleolus, substrate searching in transcription hubs, and active engagement on chromatin. This equilibrium is highly responsive to changes in DNA topology, allowing cells to regulate TOP2A levels. Using single molecule tracking, here we show that MYC accelerates TOP2A diffusion in cells. We explain this phenotype by demonstrating that MYC limits TOP2A self-interaction in vitro, while decreasing the size of TOP2A complexes in cells. By increasing TOP2A diffusion, MYC promotes substrate binding and increases TOP2A engagement on chromatin genome-wide, revealing the mechanism underlying MYC stimulation of TOP2A activity.

Indexed as

DNA Topoisomerases, Type IIPoly-ADP-Ribose Binding ProteinsProto-Oncogene Proteins c-mycCell NucleolusChromatinDiffusionDNAHumansProtein BindingChromatinDNADNA Topoisomerases, Type IIMYC protein, humanPoly-ADP-Ribose Binding ProteinsProto-Oncogene Proteins c-mycTOP2A protein, human

Identifiers

PMID41663397
PMCPMC12996632

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.