siRNA screen identifies synthetic lethal interactions with cisplatin and ATR inhibitor treatment.

<p>(A) Schematic of the siRNA screen. U2OS cells were transfected with siRNAs and then either left untreated or treated with 1μM ATRi, 0.5μM cisplatin, or ATRi and cisplatin. Cell viability was measured with alamar blue. (B) Viability of the non-targeting (NT) and ATR siRNA controls using the screen conditions. The values represent the mean ± SD of the three independent replicates of the screen. (C-E) The robust z-scores of treated compared with untreated cell viability were determined for each siRNA in the library for ATRi (C), cisplatin (D), and ATRi and cisplatin (E). The red circles represent the 8 unique siRNAs targeting ATR and ATRIP present in the library and the red line indicates a robust z score of -1.3. (F) Summary of the overlap of synthetic lethal relationships with ATRi, cisplatin, or ATRi and cisplatin. (G) Complete list of genes that exhibit a synthetic lethal relationship with ATRi, cisplatin, or ATRi and cisplatin. Genes with 2 or more siRNAs with robust z-scores of less than -1.3 are considered as synthetic lethal. The ATRi single-agent screen was previously published and included for comparison to the other drug treatments [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125482#pone.0125482.ref018" target="_blank">18</a>].