ATM and neoplasm: In somatic cells, the end-replication problem results in progressive telomere shortening (50–200 bp per division), culminating in replicative senescence when critical length thresholds (Hayflick limit) are breached; This triggers DNA damage response (DDR) activation through ataxia-telangiectasia mutated/ATM and rad3-related (ATM/ATR) kinases, stabilizing p53 to induce p21-mediated cell cycle arrest—a fundamental tumor-suppressive mechanism (33).