Oxidative stress can up-regulate tRNA cleavage (Thompson et al., 2008). We detected no differences in basal protein or DNA oxidation in patient fibroblasts or iNeurons compared with controls, but noted that iNeurons showed higher basal oxidation than fibroblasts, irrespective of genotype (Figure S5D-E). Therefore to determine whether CLP1R140H patient cells display heightened sensitivity to oxidative stress-induced cell death, we performed a dose-dependent cell viability assay using hydrogen peroxide. (HP). As previously reported in murine fibroblasts (Hanada et al., 2013), we found that human CLP1R140H mutant fibroblasts and iNeurons showed compromised cell survival to HP at the highest 50 uM concentration, indicating sensitivity to oxidative stress (Figure S5F-G).
