Reactive oxygen species (ROS) are essential for neutrophil extracellular trap (NET) formation or NETosis. This paper investigates how ROS induces NETosis. The authors demonstrate that NADPH oxidase-dependent NETosis leads to DNA damage, resulting in the nuclear translocation of proliferating cell nuclear antigen (PCNA), a key DNA repair protein. Inhibition of the DNA repair complex assembly suppresses NETosis. Excess ROS induces NETosis by causing DNA damage (oxidizing guanine to 8-oxoguanine) and activating the subsequent DNA repair pathway, leading to chromatin decondensation.