Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations.
Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations.
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DOI：
10.1038/s41467-018-02894-w
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发表时间：
2018-02-07
影响因子：
16.6
通讯作者：
Legube G
中科院分区：
文献类型：
--
作者：
Cohen S;Puget N;Lin YL;Clouaire T;Aguirrebengoa M;Rocher V;Pasero P;Canitrot Y;Legube G
共济失调伴眼用不能2（AOA-2）和肌萎缩侧索硬化（ALS 4）是由编码senataxin（SETX）的基因突变引起的神经系统疾病，SETX是一种假定的RNA：DNA解旋酶，参与转录和维持基因组完整性。在这里，使用ChIP，然后进行高通量测序（ChIP-seq），我们报告说，senataxin被招募在DNA双链断裂（DSB）时，它们发生在转录活性位点。全基因组作图揭示了RNA：DNA杂交体在DSB侧翼染色质上积累，但在DNA末端附近显示出狭窄的DSB诱导的耗尽，与senataxin结合一致。虽然既不需要切除，也不及时修复DSB，senataxin被发现促进Rad 51招聘，以尽量减少非法重新连接的远端DNA末端和维持细胞活力后DSB生产的活性基因。我们的数据表明，senataxin在DSB中发挥作用，以限制易位并确保细胞活力，为AOA 2/ALS 4神经病变提供了新的见解。最近的研究表明，RNA在DNA双链断裂修复中起着关键作用。在这里，作者确定了解旋酶senataxin参与DNA修复和解决DNA双链断裂时形成的RNA：DNA杂交体。
Ataxia with oculomotor apraxia 2 (AOA-2) and amyotrophic lateral sclerosis (ALS4) are neurological disorders caused by mutations in the gene encoding for senataxin (SETX), a putative RNA:DNA helicase involved in transcription and in the maintenance of genome integrity. Here, using ChIP followed by high throughput sequencing (ChIP-seq), we report that senataxin is recruited at DNA double-strand breaks (DSBs) when they occur in transcriptionally active loci. Genome-wide mapping unveiled that RNA:DNA hybrids accumulate on DSB-flanking chromatin but display a narrow, DSB-induced, depletion near DNA ends coinciding with senataxin binding. Although neither required for resection nor for timely repair of DSBs, senataxin was found to promote Rad51 recruitment, to minimize illegitimate rejoining of distant DNA ends and to sustain cell viability following DSB production in active genes. Our data suggest that senataxin functions at DSBs in order to limit translocations and ensure cell viability, providing new insights on AOA2/ALS4 neuropathies. Recent studies suggest key roles of RNA in DNA double-strand breaks repair. Here the authors identify the helicase senataxin to be involved in DNA repair and resolve RNA:DNA hybrids forming at DNA double-strand breaks.
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DOI：
10.1016/j.tig.2016.10.002
发表时间：
2016-12
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Chédin F
通讯作者：
Chédin F
影响因子：
16.8
作者：
Chen PB;Chen HV;Acharya D;Rando OJ;Fazzio TG
通讯作者：
Fazzio TG
影响因子：
14.8
作者：
Chailleux, Catherine;Aymard, Francois;Trouche, Didier
通讯作者：
Trouche, Didier
影响因子：
16.8
作者：
Dhir, Ashish;Dhir, Somdutta;Proudfoot, Nick J.;Jopling, Catherine L.
通讯作者：
Jopling, Catherine L.
影响因子：
16
作者：
Hatchi, Elodie;Skourti-Stathaki, Konstantina;Ventz, Steffen;Pinello, Luca;Yen, Angela;Kamieniarz-Gdula, Kinga;Dimitrov, Stoil;Pathania, Shailja;McKinney, Kristine M.;Eaton, Matthew L.;Kellis, Manolis;Hill, Sarah J.;Parmigiani, Giovanni;Proudfoot, Nicholas J.;Livingston, David M.
通讯作者：
Livingston, David M.