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Fig. 6 | Journal of Hematology & Oncology

Fig. 6

From: Hepatic NOD2 promotes hepatocarcinogenesis via a RIP2-mediated proinflammatory response and a novel nuclear autophagy-mediated DNA damage mechanism

Fig. 6

NOD2 activation inhibits DNA damage repair via lamin A/C degradation. a, b MDP (10 μg/ml) treatment inhibited 53BP1 recruitment to the DNA lesion sites in DEN-treated (100 μg/ml) hepatocytes. Representative images (a) and quantification (b) of γ-H2AX/53BP1 overlapping foci, n = 3. Immunofluorescence showed co-localization (yellow) of 53BP1 (green) and γ-H2AX (red). c, d The inhibitory effect of MDP (10 μg/ml) on 53BP1 recruitment is NOD2-dependent and can be reversed by lamin A/C overexpression (OE) in DEN-treated (100 μg/ml) hepatocytes. Representative images (c) and quantification (d) of γ-H2AX/53BP1 overlapping foci, n = 3. e MDP (10 μg/ml) treatment NOD2-dependently decreased chromatin-bound SITR6 in DEN-treated (100 μg/ml) hepatocytes, which was restored by lamin A/C overexpression. Cell lysates were fractionated to determine chromatin-bound Sirt6 levels. Bar graph shows the densitometric analyses of chromatin Sirt6 bands relative to Histone 3, n = 3. Dt, detergent-extractable fraction; Rn, RNase-extractable fraction; Chr, purified chromatin fraction, indicated in blue. f MDP (10 μg/ml) treatment NOD2-dependently decreased NHEJ efficiency, which was reversed by lamin A/C overexpression, n = 3. Data were shown as mean ± SD, and significance was determined using ordinary two-way (b) or one-way ANOVA with a Sidak test (d, e) and Student’s t test (f). *P < 0.05, **P < 0.01, n.s., not significant. Scale bar, 5 μm

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