ArticleNature communications2024
Osmotic disruption of chromatin induces Topoisomerase 2 activity at sites of transcriptional stress.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Hyperosmotic stress induces PARP1-mediated HPF1-dependent mono(ADP-ribosyl)ation.FEBS letters · 2026Article
- G-quadruplex structures as regulators of cellular processes and drivers of genome instability in cancer.Critical reviews in biochemistry and molecular biology · 2026Review
- DNA topological regulation in RNA polymerase II transcription.Cellular & molecular biology letters · 2026Review
- CRAMP1-dependent histone H1 biogenesis is essential for topoisomerase II inhibitor tolerance.Molecular cell · 2025Article
- Spo11: from topoisomerase VI to meiotic recombination initiator.Biochemical Society transactions · 2025Review
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Authors and funding
5 authors.
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Abstract
Transcription generates superhelical stress in DNA that poses problems for genome stability, but determining when and where such stress arises within chromosomes is challenging. Here, using G1-arrested S. cerevisiae cells, and employing rapid fixation and ultra-sensitive enrichment, we utilise the physiological activity of endogenous topoisomerase 2 (Top2) as a probe of transcription-induced superhelicity. We demonstrate that Top2 activity is surprisingly uncorrelated with transcriptional activity, suggesting that superhelical stress is obscured from Top2 within chromatin in vivo. We test this idea using osmotic perturbation-a treatment that transiently destabilises chromatin in vivo-revealing that Top2 activity redistributes within sub-minute timescales into broad zones patterned by long genes, convergent gene arrays, and transposon elements-and also by acute transcriptional induction. We propose that latent superhelical stress is normally absorbed by the intrinsic topological buffering capacity of chromatin, helping to avoid spurious topoisomerase activity arising within the essential coding regions of the genome.
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