Estudo sobre o reparo por recombinação homóloga em diferentes linhagens de Trypanosoma cruzi

• Ano de defesa: 2015
• Autor(a) principal: Bruno Marçal Repolês
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE BIOLOGIA GERAL; Programa de Pós-Graduação em Genética; UFMG
• Palavras-chave em Português: Trypanosoma cruzi; reparo de DNA; Recombinação Homóloga; DTU's; Rad51; BRCA2; radiação ionizante; Genética; Reparo do DNA; Recombinação homóloga; Radiação Ionizante; Quebras de DNA de cadeia dupla
• Link de acesso: http://hdl.handle.net/1843/52656

cruzi and their phylogenetic relationships, phylogeny studies recently subdivided T. cruzi into six discrete taxonomic units, named T. cruzi I to T. cruzi VI. Even though reports the occurrence of recombination events are rare in the literature, it is known that they occur between populations, creating a division between hybrid and non-hybrid populations of the parasite.The Trypanosoma cruzi DNA metabolism is focus of study of our group. Repair by homologous recombination is one of the major DNA repair pathways. This pathway is responsible for dealing with breaks in the double strands of DNA, generated by external agents or the metabolism of organisms. While other organisms have other pathways, such as non-homologous end joining to deal with double strand breaks, Trypanosoma cruzi relies only on repair by homologous recombination to deal with this kind of damage, since major proteins on the non-homologous endoining pathway could not be identified. In view ofthis fact, we studied the responseto ionizing radiation, an agent capable of causing double strand breaks, in different strains of Trypanosoma cruzi. Although the parasite does not face high doses of radiation on his life cycle, it can resist to doses as high as 500Gy of ionizing radiation. It was observed, after the exposure to ionizing radiation, that non-hybrid lineages havea distinctphenotype fromhybrid linesin response tothis kind of damage. The analysis ofgenes involvedin the repairrevealeddifferences in thesequenceof certain proteinsbetweenstrains, andthe predictionof the impactof thesechanges made on HADDOCK software,showed that the interactionbetween the proteinsofeach straincould bedifferent. Also,the basal levels oftranscripts of the proteins BRCA2 and Rad51, essentialto the process,are differentbetween thestrainscouldmean the differenceinobservedphenotype.We also demonstratethat cell signalingis quick andimportant tothe repair process, since the inhibitionofsignaling pathwaysisable to delaythe resumptionofgrowthafter irradiation