POLG and infection: Wild-type and mutator fibroblasts were infected with each lentivirus, and 5 days after lentiviral expression, cells were infected with Ad-mitoScaI-HA and collected at 1, 2, 5, and 10 days post-infection. Quantification of the relative levels of mtDNA showed similar levels of depletion following DSBs in the lenti-WT-Polg and lenti-R920H-Polg infected cells, suggesting that the polymerase activity of POLG is not required for the fast degradation of the linear mtDNA fragments (Supplementary Fig. 3).