Once phosphorylated, Smad proteins become activate and translocate to the nucleus, ultimately inducing the transcriptional activation of downstream target genes.7, 8, 9 To date, numerous studies have demonstrated that aberrant TGF-β/Smad signaling is involved in tumor metastasis, epithelial–mesenchymal transition (EMT) and DNA damage response.10, 11, 12 For example, Smad2 and Smad7 have been reported to participate in DNA damage response in an ataxia-telangiectasia mutated (ATM)-dependent manner. The gene discussed is ATM; the disease is neoplasm.