Inhibition of HPRT1-mediated AICA catalysis by HPRT1 depletion or 6-MP treatment and expression of RRM1 T52A exacerbated TMZ-induced DNA damage by attenuating DNA damage repair, leading to increased cell apoptosis and sensitization of GBM to TMZ treatment in mice (Supplementary Fig. 13). This evidence concerns the gene HPRT1 and glioblastoma.