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 approximately 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.
Li
T K
TK
Department of Pharmacology, University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Chen
A Y
AY
Yu
C
C
Mao
Y
Y
Wang
H
H
Liu
L F
LF
D004249:DNA Damage / Q000187:drug effects; D053938:DNA Fragmentation; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016296:Mutagenesis; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D013713:Teniposide / Q000494:pharmacology; D013997:Time Factors; D020298:U937 Cells
D019384:Nucleic Acid Synthesis Inhibitors; D016877:Oxidants; D013713:Teniposide; D006861:Hydrogen Peroxide; D004250:DNA Topoisomerases, Type II