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Loopholes in the DNA contract kill neurons

Nature Neuroscience volume 20, pages 1192–1194 (2017)Cite this article

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Hexanucleotide repeat expansions in C9orf72 gene locus create double jeopardy, first by leading to DNA–RNA R-loops that spawn double-strand breaks and second by the synthesis of dipeptide repeats that hinder DNA repair. This two-pronged mechanism may explain neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia.

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Figure 1: The complex pathways from C9orf72 repeats to neuronal death.

References

  1. McKinnon, P.J. Nat. Neurosci. 16, 1523–1529 (2013).

    Article  CAS  Google Scholar 

  2. Walker, C. et al. Nat. Neurosci. 20, 1225–1235 (2017).

    Article  CAS  Google Scholar 

  3. Flores, B.N. et al. PLoS One 11, e0165084 (2016).

    Article  Google Scholar 

  4. Zhang, Y.J. et al. Acta Neuropathol. 128, 505–524 (2014).

    Article  CAS  Google Scholar 

  5. May, S. et al. Acta Neuropathol. 128, 485–503 (2014).

    Article  CAS  Google Scholar 

  6. Li, J. et al. Nat. Neurosci. 16, 1745–1753 (2013).

    Article  Google Scholar 

  7. Goodarzi, A.A., Noon, A.T. & Jeggo, P.A. Biochem. Soc. Trans. 37, 569–576 (2009).

    Article  CAS  Google Scholar 

  8. Aoki, Y. et al. Brain 140, 887–897 (2017).

    Article  Google Scholar 

  9. Boeynaems, S. et al. Mol. Cell 65, 1044–1055.e5 (2017).

    Article  CAS  Google Scholar 

  10. Schmidt, M.H. & Pearson, C.E. DNA Repair (Amst.) 38, 117–126 (2016).

    Article  CAS  Google Scholar 

  11. Kobayashi, H. et al. Am. J. Hum. Genet. 89, 121–130 (2011).

    Article  CAS  Google Scholar 

  12. Chow, H.M. & Herrup, K. Nat. Rev. Neurosci. 16, 672–684 (2015).

    Article  CAS  Google Scholar 

  13. Tse, K.H. & Herrup, K. Mech. Ageing Dev. 161 Pt A, 37–50 (2017).

    Article  Google Scholar 

  14. Suberbielle, E. et al. Nat. Neurosci. 16, 613–621 (2013).

    Article  CAS  Google Scholar 

  15. Shen, X., Chen, J., Li, J., Kofler, J. & Herrup, K. eNeuro https://dx.doi.org/10.1523/ENEURO.0124-15.2016 (2016).

    Google Scholar 

Download references

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Author notes

  1. Karl Herrup, Kai-Hei Tse and Hei-Man Chow: Karl Herrup, Kai-Hei Tse and Hei-Man Chow contributed equally to this work.

Authors and Affiliations

  1. the Division of Life Science and The State Key Lab of Molecular Neuroscience, Hong Kong University of Science and Technology, Kowloon, Hong Kong

    Karl Herrup, Kai-Hei Tse & Hei-Man Chow

  2. the Institute for Advanced Studies, Hong Kong University of Science and Technology, Kowloon, Hong Kong

    Hei-Man Chow

Authors
  1. Karl Herrup
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  2. Kai-Hei Tse
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  3. Hei-Man Chow
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Corresponding authors

Correspondence to Karl Herrup, Kai-Hei Tse or Hei-Man Chow.

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Herrup, K., Tse, KH. & Chow, HM. Loopholes in the DNA contract kill neurons. Nat Neurosci 20, 1192–1194 (2017). https://doi.org/10.1038/nn.4626

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