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.

R-Loops in Motor Neuron Diseases / M.G.L. Perego, M. Taiana, N. Bresolin, G.P. Comi, S. Corti. - In: MOLECULAR NEUROBIOLOGY. - ISSN 0893-7648. - (2018). [Epub ahead of print] [10.1007/s12035-018-1246-y]

R-Loops in Motor Neuron Diseases

M. Taiana
Primo
;
N. Bresolin
Secondo
;
G.P. Comi
Penultimo
;
S. Corti
Ultimo
2018

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.
Amyotrophic lateral sclerosis; DNA damage; Motor neuron disease; R-loops; Spinal muscular atrophy; Neuroscience (miscellaneous); Neurology; Cellular and Molecular Neuroscience
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/586538
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