Fig. 7: Deletion of Trim33 promotes Myc-induced DNA damage and delays liver tumorigenesis.

a Immunofluorescence analysis with 53bp1 antibodies in p19/Nras (Ctrl) and p19/Nras/Myc (Myc) cells expressing shCtrl or shTrim33. At least 24 cells were quantified. Scale bar = 2 μm. b Immunofluorescence analysis with pH2AX antibodies in p19/Nras/Myc cells expressing shTrim33 or shCtrl and siRNAs against E2f4, Recql or control. At least 133 cells were quantified per group. Scale bar = 5 μm. c Neutral comet assays in p19/Nras/Myc cells expressing shRNAs against Trim33 or a control sequence and siRNAs against E2f4, Recql, or control. Scale bar = 10 μm. At least 39 cells were quantified per group. d Schematic of the HDTV-based model of liver tumorigenesis. Transposon vectors encoding Myc, Nras, GFP, and shCtrl or shTrim33 are injected along with the SB transposase in the tail vein of C57BL/J mice. e Representative images of whole livers under daylight and ultraviolet light showing tumor nodules. f Kaplan–Meier survival plots for two cohorts of mice injected with shTrim33 or shCtrl (7 animals/group). Significance was determined using the log-rank test. g Representative images of IHC analysis with antibodies to Trim33 and pH2AX on FFPE sections of tumor-bearing livers. h Quantification of pH2AX-positive cells per view field in liver tumors expressing shTrim33 or shCtrl. Significance was determined by a two-tailed, unpaired t-test. a, b, c Significance was determined using Kruskal–Wallis test with Dunn’s multiple comparisons. a, b, c, h Boxplots represent median±quartiles with whiskers ranging up to 1.5-fold of the interquartile range. Source data are provided as a Source Data file.