Title |
Senataxin Plays an Essential Role with DNA Damage Response Proteins in Meiotic Recombination and Gene Silencing
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Published in |
PLoS Genetics, April 2013
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DOI | 10.1371/journal.pgen.1003435 |
Pubmed ID | |
Authors |
Olivier J. Becherel, Abrey J. Yeo, Alissa Stellati, Evelyn Y. H. Heng, John Luff, Amila M. Suraweera, Rick Woods, Jean Fleming, Dianne Carrie, Kristine McKinney, Xiaoling Xu, Chuxia Deng, Martin F. Lavin |
Abstract |
Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2), plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI). Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops), and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | <1% |
United States | 1 | <1% |
Denmark | 1 | <1% |
Unknown | 146 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 38 | 26% |
Researcher | 30 | 20% |
Student > Bachelor | 14 | 9% |
Professor > Associate Professor | 8 | 5% |
Student > Master | 8 | 5% |
Other | 25 | 17% |
Unknown | 26 | 17% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 52 | 35% |
Agricultural and Biological Sciences | 41 | 28% |
Medicine and Dentistry | 10 | 7% |
Neuroscience | 7 | 5% |
Immunology and Microbiology | 3 | 2% |
Other | 8 | 5% |
Unknown | 28 | 19% |