Fig. 4: PARP-dependent DDR-signaling is necessary for CDK12 recruitment to DNA-damaged sites. | Nature Communications

Fig. 4: PARP-dependent DDR-signaling is necessary for CDK12 recruitment to DNA-damaged sites.

From: CDK12 controls transcription at damaged genes and prevents MYC-induced transcription-replication conflicts

Fig. 4

a, b Recruitment of mCherry-CDK12 to laser-damaged sites in U2OS cells treated with ATMi (10 µM KU-5593) or ATRi (10 µM VE-821). a Irradiated areas are highlighted by a white frame. DMSO: n = 14 cells; ATMi: n = 17 cells; ATRi: n = 13 cells. The graph shows the average and the standard deviation. c Recruitment of mCherry-CDK12 to laser-damaged sites in H2AX knock-out cells. U2OS wt: n = 18 cells; U2OS KO: n = 26 cells. The graph shows the average and the standard deviation. d, e Recruitment of mCherry-CDK12 to laser-damaged sites in U2OS cells treated with 1 µM olaparib or 10 µM veliparib. d Irradiated areas are highlighted by a red frame. DMSO: n = 6 cells; veliparib: n = 27 cells; olaparib: n = 25 cells. The graph shows the average and the standard deviation. ****: P value < 0.0001 (Two way anova with sidak’s multiple comparisons test). f Nascent RNA analysis at the DNA-damaged TRE-MS2 reporter locus of U2OS-TRE-I-SceI-19 cells treated with the indicated compounds. DMSO: n = 124 cells, n = 130 cells; THZ531: 4 h n = 144 cells, n = 130 cells; THZ531: 24 h n = 150 cells, n = 146 cells; ATMi: 24 n = 132 cells, n = 115 cells; ATMi 4 h + THZ531: 24 h n = 129 cells, n = 101 cells; PARPi: n = 146 cells, n = 167 cells; PARPi 4 h + THZ531: 24 h n = 126 cells, n = 154 cells. The graph shows the average and the standard deviation. Source data are provided as a Source Data file.

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