Activation of topoisomerase II-mediated excision of chromosomal DNA loops during oxidative stress

Hydrogen peroxide (H₂O₂), a reactive oxygen species (ROS), is known to induce oxidative stress and apoptosis. U937 cells treated with H₂O₂ were shown to produce high molecular weight (HMW) DNA fragments ~50 to 100 kb in size in <1 min. The formation of these HMW DNA fragments is reversible and shown to be mediated by DNA topoisomerase II (TOP2). Following this initial event, formation of irreversible HMW DNA fragments and nucleosomal ladders occurs. Our results thus demonstrate a potential role of TOP2 in oxidative damage of DNA and apoptotic cell death.