Systems Biology Approach Identifies the Kinase Csnk1a1 as a Regulator of the DNA Damage Response in Embryonic Stem Cells

Jordi Carreras Puigvert, Louise von Stechow, Ramakrishnaiah Siddappa, Alex Pines, Mahnoush Bahjat, Lizette C. J. M. Haazen, Jesper V. Olsen, Harry Vrieling, John H. N. Meerman, Leon H. F. Mullenders, Bob van de Water, Erik H. J. Danen*

*To whom correspondence should be addressed. E-mail: e.danen{at}lacdr.leidenuniv.nl

This PDF file includes:

• Fig. S1. RNAi screen conditions and analysis of siRNAs compromising basal ES cell viability.
• Fig. S2. Transcriptomics and phosphoproteomics analysis of cisplatin response.
• Fig. S3. Cell cycle arrest, apoptosis, and DNA damage repair foci in cisplatin-treated and recovered ES cells.
• Fig. S4. Roles for ATM and ATR in ES cell sensitivity to cisplatin.
• Fig. S5. Role for TGFβ signaling in ES cell sensitivity to cisplatin.
• Fig. S6. Differentiation in ES cell DDR.
• Fig. S7. Enhanced survival after cisplatin treatment by Wnt activation and effect of Wnt triple knockdown.
• Fig. S8. Csnk1a1 knockdown efficiency.
• Fig. S9. Knockdown of Csnk1a1 suppresses cisplatin-induced loss of viability and elevates cisplatin-induced Wnt signaling.
• Fig. S10. Knockdown of NDRG1 does not affect cisplatin-mediated killing or induction of Wnt signaling.
• Fig. S11. ES cell DDR signaling network derived from the RNAi screen.
• Tables S1 to S5 legends

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Other Supplementary Material for this manuscript includes the following:

• Table S1 (Microsoft Excel format). siRNAs protecting against or sensitizing to cisplatin in ES cells identified in primary SMARTpool screen and confirmation in secondary deconvolution (single siRNA) screen.
• Table S2 (Microsoft Excel format). List of differentially phosphorylated peptides in key cisplatin-regulated signaling pathways.
• Table S3 (Microsoft Excel format). Canonical pathways enriched in functional genomics, phosphoproteomics, and transcriptomics data sets for cisplatin response in ES cells.
• Table S4 (Microsoft Excel format). Molecules identified by IPA in cisplatin response signaling networks shared in three omics data sets.
• Table S5 (Microsoft Excel format). Overlap of p53 target genes and differentially expressed genes in ES cells exposed to 10 μM cisplatin.

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© 2013 American Association for the Advancement of Science