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Loopholes in the DNA contract kill neurons

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.

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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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