ArticleCell chemical biology2022
Control of topoisomerase II activity and chemotherapeutic inhibition by TCA cycle metabolites.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- Topoisomerase 1 Activity Is Reduced in Response to Thermal Stress in Fruit Flies and in Human HeLa Cells.Biosensors · 2023Article
- SMC5/6 complex-mediated SUMOylation stimulates DNA-protein cross-link repair in Arabidopsis.The Plant cell · 2023Article
- IND-2, a Quinoline Derivative, Inhibits the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress, Apoptosis and Inhibiting Topoisomerase II.Life (Basel, Switzerland) · 2022Article
- Metabolomic and Lipidomic Profiling of Gliomas-A New Direction in Personalized Therapies.Cancers · 2022Review
- Structure, dynamics, and molecular inhibition of the Staphylococcus aureus mThe Journal of biological chemistry · 2022Article
- Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling.Science signaling · 2022Article
- Nucleolar translocation of human DNA topoisomerase II by ATP depletion and its disruption by the RNA polymerase I inhibitor BMH-21.Scientific reports · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Topoisomerase II (topo II) is essential for disentangling newly replicated chromosomes. DNA unlinking involves the physical passage of one duplex through another and depends on the transient formation of double-stranded DNA breaks, a step exploited by frontline chemotherapeutics to kill cancer cells. Although anti-topo II drugs are efficacious, they also elicit cytotoxic side effects in normal cells; insights into how topo II is regulated in different cellular contexts is essential to improve their targeted use. Using chemical fractionation and mass spectrometry, we have discovered that topo II is subject to metabolic control through the TCA cycle. We show that TCA metabolites stimulate topo II activity in vitro and that levels of TCA flux modulate cellular sensitivity to anti-topo II drugs in vivo. Our work reveals an unanticipated connection between the control of DNA topology and cellular metabolism, a finding with ramifications for the clinical use of anti-topo II therapies.
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Registered trials
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