DNA-stimulated liquid-liquid phase separation by eukaryotic topoisomerase II modulates catalytic function

Abstract
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Abstract

Type II topoisomerases modulate chromosome supercoiling, condensation, and catenation by moving one double-stranded DNA segment through a transient break in a second duplex. How DNA strands are chosen and selectively passed to yield appropriate topological outcomes - e.g., decatenation vs. catenation is poorly understood. Here we show that at physiological enzyme concentrations, eukaryotic type IIA topoisomerases (topo IIs) readily coalesce into condensed bodies. DNA stimulates condensation and fluidizes these assemblies to impart liquid-like behavior. Condensation induces both budding yeast and human topo IIs to switch from DNA unlinking to active DNA catenation, and depends on an unstructured C-terminal region, the loss of which leads to high levels of knotting and reduced catenation. Our findings establish that local protein concentration and phase separation can regulate how topo II creates or dissolves DNA links, behaviors that can account for the varied roles of the enzyme in supporting transcription, replication, and chromosome compaction.

Data availability

Dataset information was uploaded to Dryad.DOI: https://doi.org/10.5061/dryad.z08kprrgc

The following data sets were generated

1. Berger JM
2. Jeong J
3. Lee J
4. Carcamo C
5. Parker M
(2022) DNA-stimulated liquid-liquid phase separation by eukaryotic topoisomerase II modulates catalytic function
Dryad Digital Repository, doi:10.5061/dryad.z08kprrgc.

https://dx.doi.org/10.5061/dryad.z08kprrgc

Article and author information

Author details

Joshua Jeong

Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, United States

Competing interests
No competing interests declared.
Joyce H Lee

Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, United States

Competing interests
No competing interests declared.
Claudia C Carcamo

Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-2646-188X
Matthew W Parker

Department of Biophysics, The University of Texas Southwestern Medical Center, Dallas, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-7571-0010
James M Berger

Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, United States

For correspondence
jmberger@jhmi.edu

Competing interests
James M Berger, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0003-0666-1240

Funding

National Institute of General Medical Sciences (T32-GM7445-43)

Joshua Jeong

National Cancer Institute (R35-CA263778)

James M Berger

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.