2024-03-29T05:13:25Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1535162021-12-28T16:41:07Zcom_10261_11773com_10261_1col_10261_11774
DIGITAL.CSIC
author
Arcas, Aída
author
Fernández-Capetillo, Óscar
author
Cases, Ildefonso
author
Rojas, A. M.
funder
Ministerio de Economía y Competitividad (España)
funder
Association for International Cancer Research
funder
Howard Hughes Medical Institute
funder
European Research Council
funder
Ministerio de Ciencia e Innovación (España)
2017-07-26T07:41:31Z
2017-07-26T07:41:31Z
2014-04
Molecular Biology and Evolution 31(4): 940-961 (2014)
0737-4038
http://hdl.handle.net/10261/153516
10.1093/molbev/msu046
1537-1719
http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/100004435http://dx.doi.org/10.13039/100000011http://dx.doi.org/10.13039/501100000781http://dx.doi.org/10.13039/501100004837
24441036
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.
eng
openAccess
DDR emergence
DDR evolution
DDR posttranslational modifications
Emergence and Evolutionary Analysis of the Human DDR Network: Implications in Comparative Genomics and Downstream Analyses
artículo
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URL
https://digital.csic.es/bitstream/10261/153516/1/msu046.pdf
File
MD5
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application/pdf
msu046.pdf