Figure 8
From: Survivin safeguards chromosome numbers and protects from aneuploidy independently from p53
ATM and DNA-PK CS induce cell cycle arrest after Survivin-RNAi. a: Western blot analysis of HCT116 and HCT116shATM total cell lysates following Survivin-RNAi (shSurv). Included are shLuc-transduced cells as control. Red values indicate densitometric estimation of protein levels, normalized to Tubulin. b: Indirect immunofluorescence analysis of transduced SBC-2 cells showing colocalisation of activated ATM (ATM S1981) and activated DNA-PK kinase (DNA-PKCS T2609) in shSurv polyploid cells. c: Western blot of HCT116 and HCT116p53−/− cell lysates showing analysis of p53 phosphorylation sites after Survivin knockdown. d: Proposed outline of Survivin RNAi phenotype and the observed DNA-damage response signaling. e: Analysis of HCT116 and HCT116shATM cells transduced with shSurv and combined treatment with DNA-PKCS inhibitor (DNA-PK-I, 10 μM Nu7026) or DMSO. Note combined inhibition of ATM and DNA-PKcs results in a decreased accumulation of p53 and p21waf/cip protein levels and reduction of γH2AX levels.