Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing

Becherel, Olivier J., Yeo, Abrey J., Stellati, Alissa, Heng, Evelyn Y. H., Luff, John, Suraweera, Amila M., Woods, Rick, Fleming, Jean, Carrie, Dianne, McKinney, Kristine, Xu, Xiaoling, Deng, Chuxia and Lavin, Martin F. (2013) Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing. PLoS Genetics, 9 4: e1003435.1-e1003435.17. doi:10.1371/journal.pgen.1003435


Author Becherel, Olivier J.
Yeo, Abrey J.
Stellati, Alissa
Heng, Evelyn Y. H.
Luff, John
Suraweera, Amila M.
Woods, Rick
Fleming, Jean
Carrie, Dianne
McKinney, Kristine
Xu, Xiaoling
Deng, Chuxia
Lavin, Martin F.
Title Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2013-04
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1003435
Open Access Status DOI
Volume 9
Issue 4
Start page e1003435.1
End page e1003435.17
Total pages 17
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number e1003435

 
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