Evolutionary conservation of synthetic lethal interactions in HCT116 cells.

<p>(A) A yeast cancer-ortholog synthetic lethal network. Lines indicate synthetic lethal genetic interactions. Yeast genes and human orthologs are presented in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003254#pgen-1003254-t001" target="_blank">Table 1</a>. Red circles represent <i>S. cerevisiae</i> orthologs of genes mutated in cancer; blue circles indicate common interacting partners, which are referred to as “central” genes. (B–D) Representative data depicting mean percentage of remaining HCT116 cells (± SEM) treated with pooled siRNAs targeting central genes (top) and cancer genes (along <i>x</i>-axis) relative to GAPDH-silenced controls. Blue circles, siRNA targeting central gene alone. Red circles, siRNA targeting cancer gene alone. Yellow triangles, predicted viability of double siRNA treatment. Green circles, observed viability of double siRNA treatment. For raw data, please refer to . GAPDH siRNA does not significantly reduce viability relative to a non-silencing siRNA (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003254#pgen.1003254.s002" target="_blank">Figure S2A</a>). (E) Representative data depicting mean percentage viability of hTERT cells (± SEM) treated with pooled siRNAs targeting FEN1 and cancer genes (along <i>x</i>-axis) relative to GAPDH-silenced controls. Symbols are as in B. (F) Mammalian genetic interaction network. Solid grey line, interaction observed in both <i>S. cerevisiae</i> and HCT116 cells; green dashed line, interaction observed only in <i>S. cerevisiae</i>; orange dotted line, interaction observed only in HCT116 cells.