MRC1 and central nervous system cancer: Indeed, proficient MMR is required for unrepaired O6-meG lesions induced by TMZ to generate cytotoxic seDSBs, and the emergence of MMR deficiencies is a documented scenario associated with TMZ resistance in gliomas [235,236,237], suggesting that defective MMR may contribute to TMZ resistance in H3.3 (G34/R/V) pHGGs.