Notably, chronic induction of p21 in a p53-independent manner, mimicking p21 expression triggered by deregulated cytokines, hormones, or growth factors in advanced p53-mutant cancers, resulted in RS and genomic instability, reflecting the inability of PCNA to interact with and regulate the degradation of the replication licensing factors CDT1 and CDC6 [81]. The gene discussed is TP53; the disease is cancer.