Table 5

Anticancer drugs and the hypertolerant phenotype of yeast strains heterozygous for the HP gene encoding their target protein
Drug Concentration in solid medium (uM) Concentration in liquid medium (uM) Mode of action Specific HP genetic target (yeast/human) Hyper-tolerant yeast strains

Cancer in which CNV-reduction of the gene deleted

in the hypertolerant strain occurs

RAD54/RAD54L
Cycloheximide 0.36, 1.8 0.1 Inhibition of translation RIM11/GSK3B IRR1/irr1 -
Mitoxantrone 10, 25 - TOPII inhibition TOP2/TOP2A - -
NBP2/nbp2
GPD1/gpd1 Serous adenocarcinoma (NBP2)
Methotrexate 200 2, 100 Inhibition of nucleoside and purine synthesis MET7/FPGS RIM11/rim11 Renal cell carcinoma (GPD1)
Phleomycin 1, 2 0.1, 0.5 DNA strand break induction - MET7/met7 Serous adenocarcinoma
5-fluorouracil 200 2, 100 Inhibition of pyrimidine synthesis - IDP1/idp1 -
Tamoxifen 25 - Estrogen receptor antagonist - - -
NBP2/nbp2
Aminopterin 10 0.1,1, 5, 10, 50, 100 Inhibition of DNA, RNA & protein synthesis - TOP1/top1 Serous adenocarcinoma
SAHA/vorinostat 10, 20 - Histone deacetylase inhibition RPD3/HDAC2 - -
Bay 11-7085 20, 40 - NF-kB TF inhibitior; proapoptotic agent - - -
Cantharidin 30, 60 6, 30 Inhibition of PP2A TPD3 UBX4/ubx4 -
PD98059 (2'-amino-3'-methylflavone) 40, 80 4 MEK1 MAPK inhibition PBS2/MAP2K1 NBP2/nbp2 Serous adenocarcinoma
HRK1/hrk1
MLH1/mlh1
Hydroxyurea 100000, 200000 100, 1000 Inhibition of DNA synthesis; DSB induction RAD54/RAD54L STP22/stp22 Renal cell carcinoma (MLH1)
Lithium chloride - Alternative RIM11 inhibitor RIM11/GSK3B -
Caffeine 1000, 5000 - Alternative RAD54 inhibitor RAD54/RAD54L -
Methyl methanesulfonate - DNA methylation, causing DSB or stalled replication forks - -
DPI 10, 20 - NAD(P)H oxidase inhibition - -
Tert-butyl hydroperoxide (TBHP) - Free-radical generation - -
Clotrimazole 2.5, 5, 7.5 - Antifungal; increases cell wall permeability - -

de Clare and Oliver

de Clare and Oliver BMC Biology 2013 11:24   doi:10.1186/1741-7007-11-24

Open Data