Importantly, the relocalisation of FUS to nucleoli triggered by TOP1-induced breakage raises the possibility that these lesions may also be an etiological factor in ALS, a possibility supported by our observations that this response to CPT was also detected in human iPSC-derived spinal motor neurons, and by the sensitivity of ALS patient-derived fibroblasts and HeLa cells expressing ALS-associated FUS mutations to CPT. Here, TOP1 is linked to amyotrophic lateral sclerosis.