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Abstract

R loops are transient three-stranded nucleic acid structures that form physiologically during transcription when a nascent RNA transcript hybridizes with the DNA template strand, leaving a single strand of displaced nontemplate DNA. However, aberrant persistence of R-loops can cause DNA damage by inducing genomic instability. Indeed, evidence has emerged that R-loops might represent a key element in the pathogenesis of human diseases, including cancer, neurodegeneration, and motor neuron disorders. Mutations in genes directly involved in R-loop biology, such as SETX (senataxin), or unstable DNA expansion eliciting R-loop generation, such as C9ORF72 HRE, can cause DNA damage and ultimately result in motor neuron cell death. In this review, we discuss current advancements in this field with a specific focus on motor neuron diseases associated with deregulation of R-loop structures. These mechanisms can represent novel therapeutic targets for these devastating, incurable diseases.

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Acknowledgments

Joint Programme Neurodegenerative Disease (JPND) Research grant DAMNDPATHS (2014) and ARISLA grant smallRNALS (2014) to SC and the Italian Ministry of Health RF- 2013-023555764 and Regione Lombardia TRANS-ALS to GPC are gratefully acknowledged. The authors wish to thank the Associazione Centro Dino Ferrari for its support.

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Correspondence to Stefania Corti.

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Perego, M.G.L., Taiana, M., Bresolin, N. et al. R-Loops in Motor Neuron Diseases. Mol Neurobiol 56, 2579–2589 (2019). https://doi.org/10.1007/s12035-018-1246-y

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  • DOI: https://doi.org/10.1007/s12035-018-1246-y

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