FUS aggregates in ALS due to defective DNA repair

In one form of the most common motor neuron disease, amyotrophic lateral sclerosis (ALS), aggregates of the so-called FUS protein appear in the cytoplasm. FUS is involved in DNA repair and must therefore be able to shuttle correctly between the nucleus and the cytoplasm; this function can be disrupted by mutations.
In a recent publication, we were able to show that mutations in the FUS nuclear localization signal (NLS) also impair a form of DNA repair (PARP-dependent DNA damage response, DDR), which further promotes mislocalization of FUS. This puts DDR signaling pathways in the focus of potential new therapeutic strategies in ALS.