Using p53-mutant MDA-MB-231 breast cancer cells treated with leflunomide and p53-deficient 4T1 breast cancer cells with ablated DHODH (DHODHKO cells; see Supplementary Fig. 4A, B for DHODH activity), we observed a similar effect of pyrimidine depletion on the cell cycle as found for wt p53 cells (Fig. 4a; see Fig. 1a for wt p53 cells) with arrest in early S-phase (Fig. 4b, c, Supplementary Fig. 4C), increased β-galactosidase activity (Supplementary Fig. 4D), and checkpoint activation (Fig. 4d). Here, DHODH is linked to breast carcinoma.