Figure 5 | Cell Death & Disease

Figure 5

From: PARG dysfunction enhances DNA double strand break formation in S-phase after alkylation DNA damage and augments different cell death pathways

Figure 5

Enhanced sensitivity to MMS treatment in MIAPaCa2 induced by PARG knockdown. (a) Western blot analysis of PARG in MIAPaCa2. (b) Clonogenic survival assay of MIAPaCa2 after MMS treatment. We also compared the effect by PARG knockdown with PARP inhibitor PJ-34 at 5 μM and analyzed the combination effects of PARG knockdown and PJ-34. (c) Flow cytometric analysis of cell cycle distribution in MIAPaCa2. Percentages of sub-G1 fraction are shown. (d) Analysis of γH2AX foci formation in MIAPaCa2 after treatment with 0.3 mM MMS. Bar 40 μm. (e) Western blot analysis of proteins involved in the DDR response (left panel) and necrosis (left panel, bottom part) after treatment with 0.3 mM MMS in PARG knockdown MIAPaCa2. Combination effect of PARP inhibitor PJ-34 at 5 μM was also analyzed for DDR response (right panel). The values under the bands show the intensities of the bands normalized by the band of α-tubulin. (f) An induction model of different cell death pathways through common DSB increase and S-phase arrest in p53 active and defective cells. This study implies that p53-dependent response itself is not important for sensitization to alkylation DNA damage by PARG dysfunction

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