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Plos Genetics : Senataxin Plays an Essential Role with Dna Damage Response Proteins in Meiotic Recombination and Gene Silencing, Volume 9

By McKinnon, Peter J.

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Book Id: WPLBN0003953155
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Senataxin Plays an Essential Role with Dna Damage Response Proteins in Meiotic Recombination and Gene Silencing, Volume 9  
Author: McKinnon, Peter J.
Volume: Volume 9
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Historic
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Publisher: Plos

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Mckinnon, P. J. (n.d.). Plos Genetics : Senataxin Plays an Essential Role with Dna Damage Response Proteins in Meiotic Recombination and Gene Silencing, Volume 9. Retrieved from http://members.worldlibrary.net/


Description
Description : 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 crossingover 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 (Rloops), 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 Setx2/2 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.

 

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