Senataxin controls meiotic silencing through ATR activation and chromatin remodeling

Yeo, Abrey J., Becherel, Olivier J., Luff, John E., Graham, Mark E., Richard, Derek and Lavin, Martin F. (2015) Senataxin controls meiotic silencing through ATR activation and chromatin remodeling. Cell Discovery, 1 15025: 1-20. doi:10.1038/celldisc.2015.25


Author Yeo, Abrey J.
Becherel, Olivier J.
Luff, John E.
Graham, Mark E.
Richard, Derek
Lavin, Martin F.
Title Senataxin controls meiotic silencing through ATR activation and chromatin remodeling
Journal name Cell Discovery   Check publisher's open access policy
ISSN 2056-5968
Publication date 2015-09-29
Year available 2015
Sub-type Article (original research)
DOI 10.1038/celldisc.2015.25
Open Access Status DOI
Volume 1
Issue 15025
Start page 1
End page 20
Total pages 20
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Senataxin, defective in ataxia oculomotor apraxia type 2, protects the genome by facilitating the resolution of RNA–DNA hybrids (R-loops) and other aspects of RNA processing. Disruption of this gene in mice causes failure of meiotic recombination and defective meiotic sex chromosome inactivation, leading to male infertility. Here we provide evidence that the disruption of Setx leads to reduced SUMOylation and disruption of protein localization across the XY body during meiosis. We demonstrate that senataxin and other DNA damage repair proteins, including ataxia telangiectasia and Rad3-related protein-interacting partner, are SUMOylated, and a marked downregulation of both ataxia telangiectasia and Rad3-related protein-interacting partner and TopBP1 leading to defective activation and signaling through ataxia telangiectasia and Rad3-related protein occurs in the absence of senataxin. Furthermore, chromodomain helicase DNA-binding protein 4, a component of the nucleosome remodeling and deacetylase chromatin remodeler that interacts with both ataxia telangiectasia and Rad3-related protein and senataxin was not recruited efficiently to the XY body, triggering altered histone acetylation and chromatin conformation in Setx−/− pachytene-staged spermatocytes. These results demonstrate that senataxin has a critical role in ataxia telangiectasia and Rad3-related protein- and chromodomain helicase DNA-binding protein 4-mediated transcriptional silencing and chromatin remodeling during meiosis providing greater insight into its critical role in gene regulation to protect against neurodegeneration.
Keyword Senataxin
DNA damage repair
Transcription
Meiosis
Chromatin remodeling
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
School of Chemistry and Molecular Biosciences
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: Google Scholar Search Google Scholar
Created: Tue, 09 Aug 2016, 15:04:41 EST by Abrey Yeo on behalf of School of Chemistry & Molecular Biosciences