Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis

@inproceedings{Wang2018MutantFC,
  title={Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis},
  author={Haibo Wang and Wenting Guo and Joy Mitra and Pavana M Hegde and Tijs Vandoorne and Bradley J Eckelmann and Sankar Mitra and Alan E. Tomkinson and Ludo Van Den Bosch and Muralidhar L Hegde},
  booktitle={Nature Communications},
  year={2018}
}
Genome damage and defective repair are etiologically linked to neurodegeneration. However, the specific mechanisms involved remain enigmatic. Here, we identify defects in DNA nick ligation and oxidative damage repair in a subset of amyotrophic lateral sclerosis (ALS) patients. These defects are caused by mutations in the RNA/DNA-binding protein FUS. In healthy neurons, FUS protects the genome by facilitating PARP1-dependent recruitment of XRCC1/DNA Ligase IIIα (LigIII) to oxidized genome sites… CONTINUE READING
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