REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
rat anti-HA	Roche	CAT# 11867423001 (RRID:AB_390918)
rabbit anti-tubulin	abcam	CAT# ab184970
IRDye 800CW goat anti-Rat	Li-Cor	CAT# 926–32219 (RRID:AB_1850025)
IRDye 680CW goat anti-rabbit	Li-Cor	CAT# 926–68071 (RRID:AB_10956166)
Bacterial and Virus Strains
XL1Blue (cloning strain)	QB3 MacroLab	N/A
BL21- CodonPlus (DE3) RIL	Agilent	CAT# 230245
Biological Samples
Chemicals, Peptides, and Recombinant Proteins
YNB-sulfate Powder	Sunrise Science	CAT# 1538
SC complete -Glucose powder	Sunrise Science	CAT# 1486
Monosodium glutamate	Sigma-Aldrich	CAT# G1626
Geneticin Selective Antibiotic (G418 sulfate)	ThermoFisher Scientific	CAT# 10131035
Acetonitrile, Optima LC/MS grade	ThermoFisher Scientific	CAT# A955–4
Methanol, Optima LC/MS Grade	ThermoFisher Scientific	CAT# A4561
Ammonium acetate	Sigma-Aldrich	CAT# 238074
Triethylamine (TEA)	Sigma-Aldrich	CAT# 471283
Formic acid 98–100%	Fisher Scientific	CAT# 33015
Trichloroacetic acid, ACS, ≥99%	Sigma-Aldrich	CAT# T6399
kDNA	Inspiralis	N/A
Adenosine 5’-triphosphate disodium	Sigma-Aldrich	CAT# A2383
Salmon Sperm DNA, sheared	ThermoFisher Scientific	CAT# AM9680
NADH	Sigma-Aldrich	CAT# 10107735001
Pyruvate kinase/lactate dehydrogenase	Sigma-Aldrich	CAT# P0294
Phosphodiesterase I from Crotalus adamanteus venom	Sigma-Aldrich	CAT# P3243
Antarctic phosphatase	NEB	CAT# M0289
BamHI	NEB	CAT# R0136S
TEV protease	QB3 MacroLab	N/A
ScTop2	Berger Lab	N/A
HsTop2A	Berger Lab	N/A
HsTop2B	Berger Lab	N/A
Ec topo IV	Berger Lab	N/A
Etoposide, synthetic, ≥98%, powder	Sigma-Aldrich	CAT# E1383
Dexrazoxane (ICRF-187)	TCI Chemicals	CAT# D4227
ICRF-193	Sigma	CAT# I4659
D-threo-isocitrate	ChiroBlock	CAT# 40056
Critical Commercial Assays
Deposited Data
ST001658 (mass spectrometry data set)	Metabolomics Workbench	http://dx.doi.org/10.21228/M89695
Experimental Models: Cell Lines
Experimental Models: Organisms/Strains
Yeast strain: BY4741 MATα his3Δ1 leu2Δ met15Δ0 ura3Δ0	ATCC	CAT# 201388
Drug Efflux Deficient (ED) yeast strain (pdr1Δ::pdr1:Cyc8 LEU2)	Bjornsti Lab (Stepanov et al., 2008)	N/A
Yeast strain: ED- mpc1Δ (mpc1Δ pdr1Δ::pdr1:Cyc8 LEU2)	Berger lab	N/A
Yeast strain: BCY123 (eukaryotic topo II expression strain)	Berger lab	N/A
Oligonucleotides
Mpc1 deletion construct forward primer: CAGCAAACGTCAATACATCTACATATATACGTATAGATTTTATTGCACTGTGATCGACATGGAGGCCCAGAATACC	IDT DNA	N/A
Mpc1 deletion construct reverse primer: GTTTCCATCTAGTCACCTACTTCAGGTTCTTAGACTGCTCGTTTTACCAGTATAGCGACCAGCATTC	IDT DNA	N/A
TOP2 N-terminal CRISPR/Cas9 gRNA oligo: GCAGTGAAAGATAAATGATCGTTGACATGGTTAGCCGTGCGTTTTAGAGCTAGAAATAGC	IDT DNA	N/A
TOP2 C-terminal CRISPR/Cas9 gRNA oligo: GCAGTGAAAGATAAATGATCAAAAAGAATGGCGCTTTCTCGTTTTAGAGCTAGAAATAGC	IDT DNA	N/A
N-terminal 3xHA tag CRISPR/Cas9 repair template: TTTCAGTTAAAGGAGTTTATAACGACGAGCACGCCTAACCATGTACCCATACGATGTTCCTGACTATGCGGGCTATCCCTATGACGTCCCGGACTATGCAGGATCCTATCCATATGACGTTCCAGATTACGCTGGTACGATGTCAACTGAACCGGTAAGCGCCTCTGATAAATATCAGA	IDT DNA	N/A
C-terminal 3xHA tag CRISPRI/Cas9 repair template: GGAAAACCAAGGATCAGATGTTTCGTTCAATGAAGAAGATGGTACGTACCCATACGATGTTCCTGACTATGCGGGCTATCCCTATGACGTCCCGGACTATGCAGGATCCTATCCATATGACGTTCCAGATTACGCTTGAATAATATTTATCGAGAGAAAGCGCCATTCTTTTTATA	IDT DNA	N/A
Recombinant DNA
pUG6	Berger lab (Güldener et al., 1996)	N/A
pJH2972	Addgene (Anand et al., 2017)	CAT# 100956 (RRID:Addgene_100956)
pSG483	Berger lab (Corbett et al. 2005)	N/A
Software and Algorithms
GraphPad Prism	GraphPad	https://graphpad.com/scientific-software/prism/ (RRID:SCR_002798)
ImageJ	NIH	https://imagej.nih.gov/ij/ (RRID:SCR_003070)
Compound Discoverer 3.0	ThermoScientific	OPTON-30925
Other
NucleoBond Xtra Maxi Columns	Macherey-Nagel	CAT # 740414
Oasis MAX Plus Short Cartridge	Waters	CAT# 186003517
Atlantis T3 OBD Prep Column (100Å, 5μm, 10mm × 250mm)	Waters	CAT# 186008205
XBridge BEH Amide OBD Pre Column (130Å., 5μm 10mm × 250mm)	Waters	CAT# 186008263
Hypersil GOLD aQ polar endcapped C18 column	ThermoFisher Scientific	CAT# 25305
Polyhydroxyethyl A hydrophilic interaction chromatography column (200 mm × 2.1 mm, 5 μm particle size)	PolyLC	CAT# 3.54HY05--