Roles of nonhomologous end-joining pathways in surviving topoisomerase II-mediated DNA damage

Topoisomerase II is a target for clinically active anticancer drugs. Drugs targeting these enzymes act by preventing the religation of enzyme-DNA covalent complexes leading to protein-DNA adducts that include single- and double-strand breaks. In mammalian cells, nonhomologous repair pathways are critical for repairing topoisomerase II–mediated DNA damage. Because topoisomerase II– targeting agents, such as etoposide, can also induce chromosomal translocations that can lead to secondary malignancies, understanding nonhomologous repair of topoisomerase II–mediated DNA damage may help to define strategies that limit this critical side effect on an important class of anticancer agents. Using Saccharomy-ces cerevisiae as a model eukaryote, we have determine