RB1 and neoplasm: Ibarra and co-workers have reported that depletion of licensing factor MCMs induces chromosome break and gap.11 As DNA damage or chromosome instability is a common cause of cell-cycle arrest and apoptosis, one of the earliest events in DNA damage is the initiation of histone H2AX phosphorylation on Ser139 to generate γ-H2AX, which forms nuclear foci and recruits DNA repair factors.54, 55 Our results showed that SVA and ARO treatment resulted higher γ-H2AX expression in RB-deficient tumor cells than in RB-proficient tumor cells.