Diseño e implementacion de una estrategia para la identificacion y caracterizacion de nuevos genes asociados al proceso de inestabilidad genomica.

The genome is the repository of the genetic information intrinsic to any species. Genomic evolution has maintained a fine balance between stability and change. The accumulation of massive changes in very short periods of time, compromises the cell homeostasis, on the contrary, few changes in extensive periods, compromise the evolvability of organisms. In metazoans, this critic balance between stability and plasticity is achieved by complex regulatory mechanisms that maintain genomic stability over time and over successive cell divisions. The set of specific molecular events leading to the generation of genetic abnormalities is called genetic instability. When such events are taken into account from a genomic perspective, the genomic instability phenomenon arises. Genomic instability has been established in recent years as a hallmark of the carcinogenic process. Different tumor types may contain different genomic alterations, including defects in the cellular machinery that controls DNa replication, fundamental alterations in the processes that detect and repair damaged DNa, and finally, modifications in the cellular machinery responsible for the proper sister chromatids segregation during mitosis. although the phenomenon of genomic instability is common to different types of carcinomas, colorectal cancer exhibits it in a very high degree as one of its distinctive molecular alterations. Nevertheless, the functional mechanisms and cellular processes that might contribute to the occurrence of the genomic instability phenotype of cancer cells are largely unknown. Due to this, it is mandatory, the design of new methodological strategies that allow the elucidation of the genetic elements and the characterization of the molecular mechanisms that are altered when genomic instability occurs. The aim of the present research project, by means of an integrative strategy, is to identify and functionally characterize new genes associated with the genomic instability process. The newly elucidated genetic elements will be critical for the understanding of the molecular mechanisms that control neoplastic transformation from a genomic instability perspective. Likewise, the identification and functional characterization of these new elements can pinpoint novel target molecules for the development of alternative therapies to treat particular carcinomas such as colon adenocarcinomas.