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. 2021 Jul 30;49(15):8665–8683. doi: 10.1093/nar/gkab628

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© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 3. — Loss of Cyclin C/CDK8 provides ATRi and CHK1i resistance. (A) Clonogenic survivals of Ccnc/Cdk8 WT/KO Atm WT/KO mESCs treated with AZD6738, represented as AUCs (areas under the curve). Error bars = mean ± S.D (biological n = 3). Survival curves can be found in Supplementary Figure S3D. (B) Clonogenic survivals of WT and Ccnc/Cdk8 single and dual KO mESCs treated with AZD6738. Data also represented as AUCs. Error bars = mean ± SD (biological n = 3). (C) Clonogenic survivals of Ccnc/Cdk8 WT/KO Atm WT/KO mESCs treated with the CHK1 inhibitor LY2603618, represented as AUCs. Error bars = mean ± SD (biological n = 3). Survival curves can be found in Supplementary Figure S3F. (D) Clonogenic survivals of WT and CCNC KO U2-OS cells in response to AZD6738 treatment. A3/B24 clones were confirmed as WT by immunoblot analyses and genotyping after single-cell expansions of sgRNA-transfected cells. Data also represented as AUCs. Error bars = mean ± SD (biological n = 3). (E) Clonogenic survivals of WT and CDK8 KO HAP-1 cells in response to AZD6738 treatment. Data also represented as AUCs. Error bars = mean ± SD (biological n = 3). (F) Clonogenic survivals of WT and CDK8 KO HAP-1 cells, complemented with WT or kinase dead (D173A) CDK8-GFP, treated with AZD6738. Data also represented as AUCs. Error bars = mean ± SD (biological n = 3). Additional clones are shown in Supplementary Figure S5A and B. All statistical analyses were performed using a one-way ANOVA test with multiple comparisons. P-values < 0.05 (*), 0.01 (**), 0.001 (***) and 0.0001 (****) were deemed statistically significant.