Senataxin: A Putative RNA: DNA Helicase Mutated in ALS4—Emerging Mechanisms of Genome Stability in Motor Neurons
Amyotrophic lateral sclerosis type 4 (ALS4) is a rare, autosomal dominant childhood- or adolescent-onset motor neuron disease caused by genetic defects in senataxin (SETX), a putative RNA–DNA helicase. Studies on the yeast SETX ortholog Sen1 revealed its role in small RNA termination pathways. It ha...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Book Chapter |
| Language: | English |
| Published: |
IntechOpen
2020
|
| Subjects: | |
| Online Access: | https://www.intechopen.com/chapters/70609 |
| Tags: |
No Tags, Be the first to tag this record!
|
| Summary: | Amyotrophic lateral sclerosis type 4 (ALS4) is a rare, autosomal dominant childhood- or adolescent-onset motor neuron disease caused by genetic defects in senataxin (SETX), a putative RNA–DNA helicase. Studies on the yeast SETX ortholog Sen1 revealed its role in small RNA termination pathways. It has been postulated that ALS4-associated neuronal pathologies could stem from defects in RNA metabolism and altered gene expression. Importantly, SETX prevents the accumulation of R-loops, which are potentially pathogenic RNA–DNA hybrids that stem from perturbations in transcription. SETX also interacts with the tumor suppressor BRCA1 that helps promote DNA double-strand break repair by homologous recombination. As such, SETX could contribute toward the removal of harmful R-loops and DSBs in postmitotic neurons. This chapter will visit the plausible mechanistic role of SETX in R-loop removal and DNA break repair that could prevent the activation of apoptotic cell death in neurons and pathological manifestation of ALS4. |
|---|---|
| ISBN: | 978-1-83880-580-7 |
| DOI: | 10.5772/intechopen.90215 |