TDP1 and nervous system disorder: To evaluate potential defects in TOP1-induced DSB repair in TDP1-associated neurological disease SCAN1, we conducted complementation experiments in TDP1-/- RPE-1 cells using an empty vector (EV), with a wild-type TDP1 (WT), with a histidine-to-alanine mutant in the catalytic histidine 263 of TDP1 (hereafter TDP1H263A), reported to be inactive [5, 25], or with the SCAN1-associated mutation H493R (hereafter TDP1H493R), which were under the control of a doxycycline-inducible promoter (for details, see methods).