In the present study, we revealed that ATRX depletion in TP53 wild-type (wt) NB cells was associated with an increased frequency of DSBs and a subsequent RS-induced DNA damage response (DDR), which was impaired by the loss of p53 through the activation of G4 DNA helicases or the FA DNA repair pathway protein, FANCD2. The gene discussed is TP53; the disease is neuroblastoma.