Human topoisomerase II alpha and II beta interact with the C-terminal region of p53

The p53 tumor suppressor protein is a critical regulator of cell cycle prog ression and apoptosis following exposure of cells to DNA damaging agents su ch as ionizing radiation or anticancer drugs. An important group of antican cer drugs, including compounds such as etoposide and doxorubicin (Adriamyci n), interacts with DNA topoisomerase II (topo II), causing the accumulation of enzyme-DNA adducts that ultimately lead to double-strand breaks and cel l death via apoptosis. Human topo II beta has previously been shown to inte ract with p53, and we have extended this analysis to show that both topo II alpha and II beta interact with p53 in vivo and in vitro. Furthermore, we show that the regulatory C-terminal basic region of p53 (residues 364-393) is necessary and sufficient for interaction with DNA topo II. (C) 2000 Acad emic Press.