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. Author manuscript; available in PMC: 2017 Nov 22.
Published in final edited form as: Cell Rep. 2016 Nov 22;17(9):2367–2381. doi: 10.1016/j.celrep.2016.10.077

Figure 2. Dinaciclib is a transcriptional CDK inhibitor that reduces expression of genes in DNA damage response and DNA repair pathways.

Figure 2

(A) MDA-MB-231 cells were treated with the indicated concentrations of dinaciclib for 6 hrs, demonstrating reduced phosphorylation at the Ser2 and Ser5 sites of the CTD of RNA pol II. (B) Cells were collected before and after treatment with 10 nM dinaciclib for 12 hrs and changes in transcription were measured using the Affymetrix HG-U133A2 arrays. Analyses were performed in triplicate. 21% of genes were significantly downregulated in dinaciclib-treated vs. untreated samples (P < 0.05). (C) Genes statistically significantly downregulated in response to dinaciclib were analyzed by Ingenuity Pathway Analysis (IPA) software, demonstrating downregulation of DNA damage response and DNA repair pathways. (D) Expression of genes in the “Role of BRCA1 in DNA Damage Response” pathway. (E) Downregulation of expression of BRCA1 and RAD51 mRNAs in cells treated with the indicated concentrations of dinaciclib was confirmed utilizing RT-PCR. (F) Concentration-dependent reduction in expression of BRCA1, BRCA2, RAD51 and FANCD2 in cells treated with dinaciclib for 24 hrs. (G) Time-dependent reduction in expression of BRCA1 and RAD51 in response to dinaciclib. (H) Cell cycle patterns following dinaciclib exposure demonstrate the absence of G1 arrest in MDA-MB-231 cells (see also Figure S2).