Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair.
Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair.
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DOI：
10.1038/s41467-018-02893-x
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发表时间：
2018-02-07
影响因子：
16.6
通讯作者：
Bushell M
中科院分区：
文献类型：
--
作者：
Lu WT;Hawley BR;Skalka GL;Baldock RA;Smith EM;Bader AS;Malewicz M;Watts FZ;Wilczynska A;Bushell M
DNA双链断裂（DSBs）的无差错、高效修复对细胞存活至关重要。RNA与DNA损伤的解决有关，但其机制尚不清楚。在这里，我们发现miRNA生物发生酶，Drosha和Dicer，从多个途径到损伤部位控制修复因子的募集。Drosha的缺失显著降低了同源重组（HR）和非同源末端连接（NHEJ）的DNA修复。在断裂诱导的几分钟内就需要Drosha，这表明RNA加工在DNA修复中的核心和早期作用。DNA测序：RNA杂交种揭示了DNA断裂位点周围的RNA入侵以drosha依赖的方式。去除这些结构的RNA成分会导致修复受损。这些结果表明，RNA如何成为人类细胞DNA损伤修复的直接和关键介质。Drosha和Dicer影响DNA修复的机制尚不清楚。在这里，作者使用了一种高通量的方法来揭示Drosha在促进DNA受损位点的DNA:RNA杂交中的作用。
The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells. The mechanism through which Drosha and Dicer affect DNA repair is not clear. Here the authors use a high-throughput approach to uncover the role of Drosha in promoting DNA:RNA hybrids at DNA damaged sites.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1126/science.1203430
发表时间：
2011-06-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cotta-Ramusino C;McDonald ER 3rd;Hurov K;Sowa ME;Harper JW;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
14.8
作者：
Chailleux, Catherine;Aymard, Francois;Trouche, Didier
通讯作者：
Trouche, Didier
影响因子：
4.5
作者：
Groh M;Lufino MM;Wade-Martins R;Gromak N
通讯作者：
Gromak N
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.