ING3 is required for ATM signaling and DNA repair in response to DNA double strand breaks

摘要

ING3 mediates resistance to DNA damage and cancer cell lines are dependent on ING3 for survival. (a) Wild type (WT) and mutant strains deleted for RAD9 (rad9Δ), YNG1 (yng1Δ), YNG2 (yng2Δ), or PHO23 (pho23Δ) were treated with various types of DNA damaging agents: 5 or 100 mM of hydroxyurea (HU), 0.5 μg/mL of bleocin (Bleo), or 10 Gy of ionizing radiation (IR). Plates were analyzed after 48 h. Summary table of the DNA damage sensitivity assay. (−) resistant, (+) to (+++) increased sensitivity, (++++) no survival. (b) Colony formation assay performed on U2OS cells transfected with siCT, siING3#1, siING3#2, or si53BP1 (53BP1 siRNA was used as a positive control) and treated with various type of DNA damaging agents: Cisplatin (CSP) (50 μM), CPT (10 nM), HU (2.5 mM), Mitomycin C (MMC) (100 ng/mL), MMS (0.5 μM), or Doxorubicin (Dox, 0.125 μM). Graph shows the number of colony formation; three independent experiment were performed. Bar graphs represent mean ± SEM (NSP > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001). c Distribution of ING genes CERES score in cancer cell lines (v.2018Q1 of Avana 1.0 library). d Mean CERES score of ING genes in cancer cell lines (***P < 0.0001; n = 391 per group)