Fig. 2: CDK12 silencing or inhibition rescues transcription at DNA-damaged genes.

a, b Bee swarm plots of single-cell nascent-RNA synthesis (by EU incorporation) in mock or UV-irradiated cells. Cells were pulsed with 0.5 M EU for 20 min. before collection. a U2OS cells: siLuc n = 1965 cells; siCDK12#1: n = 2320 cells; siCDK12#2: n = 3446 cells; siLc+UV: n = 2363 cells; siCDK12#1 + UV: n = 5003 cells; siCDK12#2 + UV: n = 2806 cells. b RPE1 cells: siLuc n = 4100 cells; siCDK12#1 n = 4090 cells; siCDK12#2: n = 4482 cells; siLc+UV: n = 5503 cells; siCDK12#1 + UV: n = 2897 cells; siCDK12#2 + UV: n = 4057 cells. ****: P value < 0.0001 (Kruskal Wallis test with multiple comparisons). c WB analysis. VCL is a loading control. d, e Representative IF-images (d) and bar plot (e) of the colocalization of mCherry-tTA-ER and YFP-MS2 signals upon silencing of CDK12 in U2OS-TRE-I-SceI-19 cells. Where indicated, cells were transfected with I-SceI (+SceI) to induce DSBs on the TRE-MS2 reporter. Average of two independent experiments. siRLuc: n = 58 cells, n = 109 cells; siCDK12#1: n = 97 cells, n = 117 cells; siCDK12#2: n = 48 cells, n = 94 cells; siRLuc+SceI: n = 64 cells, n = 109 cells; siCDK12#1+SceI: n = 70 cells, n = 102 cells; siCDK12#2+SceI: n = 67 cells, n = 76 cells. The error bar is the standard deviation. f, g As in d, e, but upon inhibition of CDK12. Average of two independent experiments. DMSO: n = 159 cells, n = 124 cells; THZ531: n = 123 cells, n = 93 cells; DMSO+SceI: n = 113 cells, n = 87 cells; THZ531+SceI: n = 111 cells, n = 96 cells. The error bar is the standard deviation. Source data are provided as a Source Data file.