Siddhartha Tyagi

Figure S3 shows MYC-induced apoptosis and cell death in early and late timepoints, ectopic expression of BCL2 and its impact on MYC-induced RNA decay, gene expression changes upon DIS3L knockdown in MYC-hyperactivated conditions, and expression of exosome components upon MYC-induction.

Figure S4 shows DIS3L mutation in human tumors, evolutionary action score of tumor-derived mutation in DIS3L, genomic alteration of MYC and DIS3L in human breast cancer, expression of DIS3L mRNA in human breast tumors, and expression of genes in ribonucleotide catabolism and synthesis upon DIS3L knockdown.

Table S1 is the list of candidate facilitator genes of MYC-induced cell death. Table lists the candidate facilitators of MYC-induced cell death discovered through the MYC-specific loss of function genetic screen.

Table S4 shows predictions of hypothetical purine nucleotide flux.

Figure S1 shows PCA of human breast tumors, hallmark MYC signature score for human breast tumors, expression of MYC-target NECTIN4, schematic for purine ribonucleotide catabolism, concentrations of nucleotides in physiological conditions, prediction of hypothetical purine nucleotide flux, MYC-induced cell death in MYC-ER HMECs, and candidate facilitators of MYC-induced cell death.

Figure S5 shows expression of MCL1 upon DIS3L knockdown, effect of XDH inhibition on MYC-induced cell death, effect of xanthosine on TNBC apoptosis, ROS and MYC-induced cell death, MYC-induced cell death upon HPRT1 knockdown, and expression of HPRT1 upon knockdown, and effect of DIS3L knockdown on TNBC xenografts.

Figure S2 shows MYC-induced cell death in MYC-ER HMECs with DIS3L, EXOSC2, EXOSC8 and DIS3 knockdown, expression of DIS3L, EXOSC2, EXOSC8 and DIS3 upon knockdown, and MYC-induced EU incorporation in MYC-hyperactivated conditions.

Figure S6 shows 6-mercaptopurine dose curve in various cell lines, effect of 6-mercaptopurine on purine catabolite abundance in TNBC cells, effect of XDH knockdown on 6-mercaptopurine induced cell death, and 6-mercaptopurine- induced effect on cell viability upon purine nucleotide supplementation.

Table S3 shows evolutionary Action analysis of tumor-derived mutation in DIS3L.

Table S2 shows gene ontology analysis of candidate facilitator genes of MYC-induced cell death.