Accumulation of TOP1- or TOP2-mediated PDBs cause neurological disease in humans (Katyal et al., 2014, Alagoz et al., 2013, El-Khamisy et al., 2005, Gómez-Herreros et al., 2014, Walker and El-Khamisy, 2018) and has been widely exploited in cancer chemotherapy (Alagoz et al., 2014, Ashour et al., 2015, Das et al., 2014, Meisenberg et al., 2017, Rehman et al., 2018). The gene discussed is TOP1; the disease is cancer.