Caracterización del evento celular inestabilidad genómica bajo un contexto de genómica comparativa

Abstract

Cells have evolved control mechanisms and repair machinery that prevent DNA damage from occurring during cell division. Thus, it is possible to maintain a cellular homeostasis and the chances that the genetic information that will be inherited to the offspring incorporates mutations are avoided. But even with this tight control, defects in the regulation of any of these mechanisms can occur, resulting in the emergence of genomic instability. When genomic instability arises, there is evidence of a progressive increase in the acquisition of disorders or variations in the genome, either at the nucleotide or chromosome level. This predisposes cells to a state of unregulated cell division, with a high probability of neoplastic transformation. Many studies show and relate the imbalances in genetic information with processes involved in tumorigenesis. However, it is unknown other biological processes that might be directed associated with genomic instability. During the development of this project, a characterization of the cellular event of genomic instability was performed under a comparative genomics context. For this, bioinformatics tools such as Cytoscape, BiNGO, Pathway Studio; and WEB resources or databases such as molbiotools, Orthologous Matrix, GeneCards, Phenologs, The Human Phenotype Ontology, GWAS Catalog and TAIR were used. It was found that the cellular event under study is genetically linked with 466 genes in humans; 167 out of these 466 genes have orthologs in Arabidopsis thaliana. For each of these gene-sets, relevant biological processes were identified for shared human-Arabidopsis orthologs and for gene-sets exclusively occurring in humans or plants. For the latter, relationships between phenotypes were established, genetic conformations for biological processes were expanded and 6 potential phenologs were found using the Phenologs algorithm proposed by McGary and collaborators. Additionally, with the genes identified in the shared biological processes, a functional enrichment analysis was carried out in Pathway Studio® software and the functional diversity that constitutes the cellular event genomic instability was extended beyond the archetypical biological processes. The implemented strategy, allowed to provide evidence that the biological processes "DNA repair" and "replication stress" are crucial in the emergence and establishment of nucleotide mismatches in the genome. Thus, using a comparative approach, a characterization of the cellular event genomic instability was generated, finding elements and relationships that transcend the cancer perspective.