TOP1 and Cerebellar atrophy: Given that the loss of TDP1 leads to an age-dependant and progressive cerebellar atrophy, and that cerebellar neurons or primary astrocytes derived from Tdp1−/− mice display an inability to rapidly repair DNA SSBs associated with Top1-DNA complexes or oxidative damage [18], we generated Setx−/−Tdp1−/− double mutants to investigate whether the compounded defects would induce or exacerbate R-loop formation and trigger a neurological phenotype.