Extended Data Fig. 3: Glucose restriction specifically represses replication stress and apoptosis caused by pyrimidine synthesis inhibition.
a, Immunoblot analysis of replication stress and apoptosis in Jurkat cells treated with brequinar ± uridine in high and low glucose for 48 hr. b, Immunoblot analysis of replication stress and apoptosis in Jurkat cells treated with brequinar (400 nM), RTX (20 nM) or HU in high and low glucose for 48 hr. c, Immunoblot analysis of replication stress and apoptosis in Jurkat cells co-treated with RTX (10 nM) and multiple doses of 3-DAU for 48 hr. d, Proliferation of Jurkat cells following RTX washout (left) and immunoblot analysis of replication stress and apoptosis in those cells (right), n = 3 biological replicates. e, Immunoblot analysis of replication stress and apoptosis in Jurkat cells treated with brequinar (400 nM), RTX (10 nM), HU (0.5 mM), or aphidicolin (2 μg/ml) for 48 hr in HPLM containing high or low glucose. f, Immunoblot analysis of replication stress and apoptosis in Jurkat cells treated with MPA ± 50 μM guanosine (left) or 20 μM MPA ± 50 μM Z-VAD (right) in high and low glucose for 48 hr. g, Immunoblot analysis of replication stress and apoptosis in Jurkat cells treated with actinomycin D (ActD) ± Z-VAD (50 μM) in high and low glucose for 48 h. h, Colonies formed from RTX-treated HCT116 cells in high and low glucose. i,j, Immunoblot analysis of replication stress and apoptosis in Jurkat cells treated with etoposide (1.5 μM), doxorubicin (100 nM), cisplatin (5 μg/ml) for 24 hr (i) or aphidicolin for 48 h (j) in high and low glucose. Statistical significance is determined by two-sided Student’s t-test (d). ns: not significant.
