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The Dna Damage Response: Domain-based analysis of its components

AutorArcas, Aída; Cases, Ildefonso; Rojas, A. M.
Fecha de publicaciónsep-2014
CitaciónXII Symposium on Bioinformatics (2014)
ResumenThe DNA damage response (DDR) is a crucial signaling network that preserves the integrity of the genome. Although extensive work has been conducted in particular proteins of the DDR, few evolutionary studies have been done to understand the origin of these proteins and to provide insightful clues into how this concerted system of pathways has been acquired in eukaryotes. In this work we study at a domain level the orthologous sequences of 118 human DDR proteins to establish the domain repertoire involved in the DDR, to analyze the conservation of domains in different organisms, and to determine the acquisition of novel functions due to diverse domain architectures reflecting differences at the species level. Also, we intend to identify whether there are domains enriched in DDR-related functions. We have identified DDR orthologous sequences with InParanoid in a comprehensive set of species. The domain composition of the orthologous DDR sequences was analyzed using HMMER and the Pfam database. Also, manual identification of remote homologous domains in orthologous proteins without detected Pfam domains was performed. We constructed phylogenetic protein and domain profiles and clustered them to identify proteins and domains that have appeared consistently in evolution, respectively. Besides, domain enrichment analyses were performed and the distribution of domains in DDR functional tiers was analysed. Our results show that most components of the DDR appear to be specific to the eukaryotic lineage. This specificity is related to the acquisition of novel domains that increase the pathways complexity in terms of fine-tuning and extend the interaction repertoire of DDR proteins to cross-talk with closely related pathways. Also, along evolution lineage-specific and domain rearrangement events may have included novel functions in various organisms, mainly in plants.
DescripciónTrabajo presentado en el XII Symposium on Bioinformatics (XII Jornadas de Bioinformática), celebrado en Sevilla del 21 al 24 de septiembre de 2014.
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