Extended Data Fig. 7: CDS2 dosage and catalytic activity govern synthetic lethality.
a, Graph depicting RNA quantification by qPCR of 10-d CDS2 knockdown in ectopic CDS1-restored BLM cells from the experiment depicted in Fig. 7b. Two-way ANOVA followed up by Šidák’s test was used. n = 3 replicates for 1 cancer cell line for 3 shCDS2. b, Plot depicting time until palpable tumors were formed for the experiment in Fig. 7c. Student’s t-test was used. n = 9 NOD-scid Il2rγ-null mice per group. c, Alignment of a part of the human CDS2 amino acid sequence with bacterial TmCdsA showing they both contain an aspartic acid (red box). Added on top is the conservation across 150 species of each of the presented amino acids as determined by ConSurf62. d, The computationally predicted (Alphafill) ion binding to the aspartic acid highlighted in panel c for bacterial TmCdsA and human CDS263. The bacterial structure was validated in a previous report. In a: ***P<0.001.
