Final Report Summary - DSBRECA (Relevance of double strand break repair pathway choice in human disease and cancer)
The project DSBRECA is rooted in the idea that cancer and other genetically inherited diseases occur when the balance between different DNA repair mechanisms is altered. Thus, in such scenario DNA lesions are repaired, but not using the best repair mechanism for that specific cellular stage, causing an increase in the appearance of mutations. Although most DNA repair mechanism are well characterized, the cellular network that control the balance between them is mostly unknown due to the lack of genetic tools to analyze it. We tried to tackle this complicated issue by creating new genetics tools to study the balance between the two main repair pathways involved in the repair of DNA breaks. It is based in the induction of an artificial break in a DNA molecule in an inducible and controlled way. Such break it is then repaired by the cells using one of two alternative mechanisms, but rendering a distinct signal in each case: i.e. the accumulation of green or red fluorescence within the cell. By calculating the ratio between green and red cells we can measure the balance between different repair mechanisms. Also, we can manipulate cells, genetically, chemically or physically, to understand which specific factors control the balance between repair pathways.
Thanks to this novel tool, we have been able to find and characterize new cellular factors that are relevant for this process. We have done that by combining chemical treatments with molecules currently in cancer clinical trials or genetic disruption of human genes. Thus, we have uncovered new cellular pathways that control the repair of DNA breaks and we have explored their relevance for cancer appearance and treatment.
Thanks to this novel tool, we have been able to find and characterize new cellular factors that are relevant for this process. We have done that by combining chemical treatments with molecules currently in cancer clinical trials or genetic disruption of human genes. Thus, we have uncovered new cellular pathways that control the repair of DNA breaks and we have explored their relevance for cancer appearance and treatment.