Summary of project PR001063

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001063. The data can be accessed directly via it's Project DOI: 10.21228/M89695 This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001063
Project DOI:doi: 10.21228/M89695
Project Title:Control of Topoisomerase II Activity and Chemotherapeutic Inhibition by TCA Cycle Metabolites
Project Summary:Topoisomerase II (topo II) is essential for disentangling newly-replicated chromosomes. DNA unlinking involves the physical passage of one DNA duplex through another and depends on the transient formation of double-strand DNA breaks, a step exploited by frontline chemotherapies 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 works reveals an unanticipated connection between the control of DNA topology and cellular metabolism, a finding with important ramifications for the clinical use of anti-topo II therapies.
Institute:Johns Hopkins University
Last Name:Mosher
First Name:Eric
Address:725 North Wolfe Street, Biophysics 307

Summary of all studies in project PR001063

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST001658 Control of Topoisomerase II Activity and Chemotherapeutic Inhibition by TCA Cycle Metabolites Saccharomyces cerevisiae Johns Hopkins University MS 2021-02-17 1 3 Uploaded data (1G)*