POLG and cancer: A similar state exists in mouse cells except that exon 2 of PolgA undergoes extensive DNA methylation in order for PolgA to be expressed.9 Nevertheless, cancer cells are unable to modulate DNA methylation at this location and fail to differentiate.17 Interestingly though, we further demonstrate that mtDNA-depleted cancer cells can modulate DNA demethylation at exon 2 of POLGA to enable replenishment of mtDNA to pre-depleted levels, which suggests that each tumour cell type has a defined number of mtDNA copies or set point.