Leucine carboxyl methyltransferase (LCMT-1), a specific SAM-dependent enzyme, catalyzes the methylation of PP2A, and here, we observed that irradiation of breast cancer cells induced IR-dependent methylation of PP2A, which resulted in the catalytic activation of this phosphatase (Supplementary Fig. S2 and Fig. S11). Here, PTPA is linked to breast cancer.