Emergence and evolutionary analysis of the human DDR network: implications in comparative genomics and downstream analyses.
Emergence and evolutionary analysis of the human DDR network: implications in comparative genomics and downstream analyses.
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DOI：
10.1093/molbev/msu046
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发表时间：
2014-04
影响因子：
10.7
通讯作者：
Rojas AM
中科院分区：
文献类型：
--
作者：
Arcas A;Fernández-Capetillo O;Cases I;Rojas AM
DNA损伤反应（DDR）是维持基因组完整性的重要信号网络。该网络由不同但经常重叠的子网组成，其中不同的组件在精确的空间和时间场景中实现不同的功能。为了了解这些元素是如何在人类中组装在一起的，我们对47个选定的物种进行了比较基因组分析，利用系统的系统发育分析和估计的基因年龄来追溯它们的出现。还研究了翻译后修饰对DDR复杂调控的贡献。这是第一次对整个DDR子网的演变进行系统的分析。我们的研究结果表明，DDR核心主要围绕代谢活动构建，在真核生物出现后不久就出现了，随后通过复杂的进化过程出现了额外的调节能力。潜在的关键翻译后修饰也在那时出现，相互作用对优先出现在同一进化时间，尽管修饰通常导致随后获得新的靶标。我们还在真菌、植物和节肢动物的调控网络的基本模块中发现了广泛的基因丢失，这对于它们作为DDR研究的模式生物的有效性很重要。
The DNA damage response (DDR) is a crucial signaling network that preserves the integrity of the genome. This network is an ensemble of distinct but often overlapping subnetworks, where different components fulfill distinct functions in precise spatial and temporal scenarios. To understand how these elements have been assembled together in humans, we performed comparative genomic analyses in 47 selected species to trace back their emergence using systematic phylogenetic analyses and estimated gene ages. The emergence of the contribution of posttranslational modifications to the complex regulation of DDR was also investigated. This is the first time a systematic analysis has focused on the evolution of DDR subnetworks as a whole. Our results indicate that a DDR core, mostly constructed around metabolic activities, appeared soon after the emergence of eukaryotes, and that additional regulatory capacities appeared later through complex evolutionary process. Potential key posttranslational modifications were also in place then, with interacting pairs preferentially appearing at the same evolutionary time, although modifications often led to the subsequent acquisition of new targets afterwards. We also found extensive gene loss in essential modules of the regulatory network in fungi, plants, and arthropods, important for their validation as model organisms for DDR studies.
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影响因子：
64.5
作者：
Fekairi S;Scaglione S;Chahwan C;Taylor ER;Tissier A;Coulon S;Dong MQ;Ruse C;Yates JR 3rd;Russell P;Fuchs RP;McGowan CH;Gaillard PHL
通讯作者：
Gaillard PHL
影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
10.5
作者：
Bansbach, Carol E.;Betous, Remy;Cortez, David
通讯作者：
Cortez, David
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ