DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci.
DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci.
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DOI：
10.1093/nar/gkac843
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发表时间：
2022-10-14
影响因子：
14.9
通讯作者：
Bushell, Martin
中科院分区：
文献类型：
--
作者：
Bader, Aldo S.;Luessing, Janna;Hawley, Ben R.;Skalka, George L.;Lu, Wei-Ting;Lowndes, Noel F.;Bushell, Martin
具有RNA结合活性的蛋白质越来越多地参与DNA损伤反应(DDR)。此外，DNA：RNA-杂交体在DNA双链断裂(DSB)周围迅速产生，对于有效的修复是必不可少的。在这里，使用蛋白质组数据的荟萃分析，我们识别了新的DNA修复蛋白，并表征了DDX17在DNA修复中的新角色。我们发现DDX17对细胞生存和DNA修复都是必需的，以响应许多诱导DSB的药物。对DSB修复因子募集到损伤部位的分析表明，DDX17在DSB泛素级联反应的早期起到了作用。R-环的全基因组图谱显示，虽然DDX17促进了DSB位点周围DNA：RNA-杂交体的形成，但这一作用仅限于具有低水平先前存在的杂交体的基因座。我们认为，DDX17通过催化DSB诱导的杂交体的形成，促进在形成DNA：RNA杂交体时低效的DSB修复，从而允许损伤反应的传播。
Proteins with RNA-binding activity are increasingly being implicated in DNA damage responses (DDR). Additionally, DNA:RNA-hybrids are rapidly generated around DNA double-strand breaks (DSBs), and are essential for effective repair. Here, using a meta-analysis of proteomic data, we identify novel DNA repair proteins and characterise a novel role for DDX17 in DNA repair. We found DDX17 to be required for both cell survival and DNA repair in response to numerous agents that induce DSBs. Analysis of DSB repair factor recruitment to damage sites suggested a role for DDX17 early in the DSB ubiquitin cascade. Genome-wide mapping of R-loops revealed that while DDX17 promotes the formation of DNA:RNA-hybrids around DSB sites, this role is specific to loci that have low levels of pre-existing hybrids. We propose that DDX17 facilitates DSB repair at loci that are inefficient at forming DNA:RNA-hybrids by catalysing the formation of DSB-induced hybrids, thereby allowing propagation of the damage response.
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DOI：
10.15252/embj.2018100158
发表时间：
2018-09-14
期刊：
The EMBO journal
影响因子：
--
作者：
Findlay S;Heath J;Luo VM;Malina A;Morin T;Coulombe Y;Djerir B;Li Z;Samiei A;Simo-Cheyou E;Karam M;Bagci H;Rahat D;Grapton D;Lavoie EG;Dove C;Khaled H;Kuasne H;Mann KK;Klein KO;Greenwood CM;Tabach Y;Park M;Côté JF;Masson JY;Maréchal A;Orthwein A
通讯作者：
Orthwein A
影响因子：
16
作者：
Beli, Petra;Lukashchuk, Natalia;Wagner, Sebastian A.;Weinert, Brian T.;Olsen, Jesper V.;Baskcomb, Linda;Mann, Matthias;Jackson, Stephen P.;Choudhary, Chunaram
通讯作者：
Choudhary, Chunaram
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：
16.6
作者：
Bayona-Feliu A;Casas-Lamesa A;Reina O;Bernués J;Azorín F
通讯作者：
Azorín F
影响因子：
14.9
作者：
Burger, Kaspar;Schlackow, Margarita;Gullerova, Monika
通讯作者：
Gullerova, Monika