IDH1 and cancer: Oncogenic mutants of isocitrate dehydrogenase 1 and 2 (IDH1/2) induce accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which impairs HR and generates heterochromatin-dependent DNA replication stress, making IDH1/2 mutant cancer cells hypersensitive to PARPi (123, 124).