Activation of p53‐dependent downstream targets, including the cyclin‐dependent kinase inhibitor CDKN1A/p21WAF1/CIP1 (p21) by dysfunctional telomeres, results in G1 cell cycle arrest and the onset of cellular senescence to potently suppresses tumor initiation and progression in vivo (Cosme‐Blanco et al., 2007; Feldser & Greider, 2007). The gene discussed is TP53; the disease is neoplasm.