Fig. 5: Nbn mutation elevates DNA damage and deactivates ATR-Chk1 signaling in liver regeneration. | npj Regenerative Medicine

Fig. 5: Nbn mutation elevates DNA damage and deactivates ATR-Chk1 signaling in liver regeneration.

From: The MRN complex maintains the biliary-derived hepatocytes in liver regeneration through ATR-Chk1 pathway

Fig. 5

a Single optical section images showing γH2AX (red), Dendra2 (green), and DAPI (blue) expressions in regenerating livers at R24h and R48h in wild-type and nbn mutant. Quantification of the number of γH2AX+ cells per liver, n = 7 larvae per group. b Schematic illustration of Mtz treatment and inhibitor treatment under HU exposure. c Western blot images of p-Chk1 in wild-type, HU-treated wild-type and HU-treated nbn mutant larvae. Note that nbn mutation abrogates the Chk1 phosphorylation upon HU treatment. d Western blot images of p-Chk2 in wild-type, HU-treated wild-type, and HU-treated nbn mutant larvae. e Confocal projection images showing the regenerating livers of Chk1 inhibitor treatment under the Tg(lfabp:DenNTR) background. f Confocal projection images showing the regenerating livers of ATR inhibitor and ATM inhibitor treatment under the Tg(lfabp:DenNTR) background. Note that ATR inhibitor but not ATM inhibitor treatment shows reduced liver regeneration in wild-type upon HU treatment. Asterisks indicate statistical significance: **P < 0.01; ***P < 0.001 using t-tests analysis when compared to control. Numbers indicate the proportion of larvae exhibiting the expression shown. Scale bars, 100 μm; error bars, ±SEM. WT wild-type, R regeneration time after the withdrawal of Mtz, DAPI 4′, 6-diamidino-2-phenylindole, HU hydroxyurea, Chk1i Chk1 inhibitor CHIR-124, ATRi ATR inhibitor VE-821, ATMi ATM inhibitor KU55933.

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