ARF binding to topo I involves the C-terminal domain of ARF [13], which is not required for its p53-dependent activity, and is enhanced by protein kinase CK2 (“CK2”)-mediated hyperphosphorylation of topo I. We have shown that such aberrant topo I phosphorylation occurs on serine 506 (PS506) and is a cancer-related abnormality that is characteristic of cancer cells expressing elevated CK2 levels [9], [14]. This evidence concerns the gene TP53 and cancer.