Senataxin protects the genome: implications for neurodegeneration and other abnormalities

Lavin, Martin F., Yeo, Abrey J. and Becherel, Olivier J. (2013) Senataxin protects the genome: implications for neurodegeneration and other abnormalities. Rare Diseases, 1 1: e25230.1-e25230.6. doi:10.4161/rdis.25230

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ328409_OA.pdf Full text (open access) application/pdf 475.07KB 27

Author Lavin, Martin F.
Yeo, Abrey J.
Becherel, Olivier J.
Title Senataxin protects the genome: implications for neurodegeneration and other abnormalities
Journal name Rare Diseases   Check publisher's open access policy
ISSN 2167-5511
Publication date 2013-06-06
Sub-type Letter to editor, brief commentary or brief communication
DOI 10.4161/rdis.25230
Open Access Status File (Publisher version)
Volume 1
Issue 1
Start page e25230.1
End page e25230.6
Total pages 6
Place of publication Georgetown, TX, United States
Publisher Landes Bioscience
Collection year 2014
Language eng
Formatted abstract
Ataxia oculomotor apraxia type 2 (AOA2) is a rare autosomal recessive disorder characterized by cerebellar atrophy, peripheral neuropathy, loss of Purkinje cells and elevated α-fetoprotein. AOA2 is caused by mutations in the SETX gene that codes for the high molecular weight protein senataxin. Mutations in this gene also cause dominant neurodegenerative disorders. Similar to that observed for other autosomal recessive ataxias, this protein protects the integrity of the genome against oxidative and other forms of DNA damage to reduce the risk of neurodegeneration. Senataxin functions in transcription termination and RNA splicing and it has been shown to resolve RNA/DNA hybrids (R-loops) that arise at transcription pause sites or when transcription is blocked. Recent data suggest that this protein functions at the interface between transcription and DNA replication to minimise the risk of collision and maintain genome stability. Our recent data using SETX gene-disrupted mice revealed that male mice were defective in spermatogenesis and were infertile. DNA double strand-breaks persisted throughout meiosis and crossing-over failed in SETX mutant mice. These changes can be explained by the accumulation of R-loops, which interfere with Holiday junctions and crossing-over. We also showed that senataxin was localized to the XY body in pachytene cells and was involved in transcriptional silencing of these chromosomes. While the defect in meiotic recombination was striking in these animals, there was no evidence of neurodegeneration as observed in AOA2 patients. We discuss here potentially different roles for senataxin in proliferating and post-mitotic cells.
Keyword Ataxia oculomotor apraxia type 2 (AOA2)
SETX gene
RNA processing
DNA double strand breaks
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Letter to editor, brief commentary or brief communication
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Chemistry and Molecular Biosciences
School of Medicine Publications
Version Filter Type
Citation counts: Google Scholar Search Google Scholar
Created: Thu, 17 Apr 2014, 15:32:13 EST by Olivier Becherel on behalf of UQ Centre for Clinical Research