In this screen, we identified 4 candidate suppressors—the lysine acetyltransferase, Esa1, the gene expression regulator, Tos4, the m6A RNA binding protein Pho92, and the cyclin-dependent kinase, Sgv1/Bur1—that rescue the caffeine-associated growth defects that are exhibited by histone H3K36 missense mutations, which are known oncogenic drivers in cancer. This evidence concerns the gene KAT5 and cancer.