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首页> 外文期刊>Cell discovery. >Senataxin controls meiotic silencing through ATR activation and chromatin remodeling
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Senataxin controls meiotic silencing through ATR activation and chromatin remodeling

机译：Senataxin通过ATR激活和染色质重塑控制减数分裂沉默

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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.
机译：Senataxin是2型共济失调动眼性失用症的缺陷，它通过促进RNA-DNA杂种（R环）的解析和RNA加工的其他方面来保护基因组。小鼠中该基因的破坏导致减数分裂重组失败和减数分裂性染色体的失活，导致男性不育。在这里，我们提供的证据表明，减数分裂期间Setx的破坏导致SUMOylation的降低和整个XY体内蛋白质定位的破坏。我们证明了senataxin和其他DNA损伤修复蛋白，包括共济失调毛细血管扩张和与Rad3相关的蛋白相互作用的伴侣，被SUMOylated，共济失调毛细血管扩张和与Rad3相关的蛋白相互作用的伴侣和TopBP1的明显下调，导致活化和信号传导缺陷共济失调的毛细血管扩张和Rad3相关蛋白在缺乏senataxin的情况下发生。此外，与共济失调毛细血管扩张和Rad3相关蛋白和senataxin相互作用的核小体重塑和脱乙酰基酶染色质重塑剂的组成部分chromodomain解旋酶DNA结合蛋白4没有被有效地募集到XY体内，从而触发了组蛋白乙酰化和染色质构象的改变。 Setx ？/？ 粗线阶段的精母细胞。这些结果表明，senataxin在共济失调毛细血管扩张和Rad3相关蛋白和染色体域解旋酶DNA结合蛋白4介导的减数分裂过程中的转录沉默和染色质重塑中起关键作用，从而提供了对其在基因调控中防止神经变性的关键作用的深入了解。

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