Since TOP1 deficiency as well as defects in the processing of TOP1-DNA lesions are widely implicated in transcription-associated genomic instability and neurodegenerative diseases3, 4, 5, 16, 18, it is possible that the genomic instability induced by SMARCA4 inactivation in human cancers is due, at least in part, to the compromised TOP1 recruitment to chromatin. The gene discussed is TOP1; the disease is cancer.