PNKP and nervous system disorder: We reported previously that cells from MCSZ patients typically exhibit reduced rate of repair of SSBs induced as a result of the abortive activity of topoisomerase 1 (TOP1): a physiologically relevant source of SSBs that are implicated in neurological disease and are substrates for both the DNA kinase and DNA phosphatase activities of PNKP (Kalasova et al., 2019, 2020; Reynolds et al., 2012).