The Action "rDNAstress" contributes to target one of the priority challenges defined by the European Union: Health, demographic changes and well-being. The main objective of this challenge is health-improving during life and increasing the welfare of society. Importantly, the proposed project is generating in-depth knowledge about genome instability in human cells to understand cancer disease. Hopefully, this project's results will help extend our knowledge about a minimal region of the human genome, named ribosomal DNA, which is essential to genome maintenance and could be a potential tool for targeting cancer cells. Furthermore, the functional role of the ribosomal DNA to synthesize ribosomes, main machinery for protein synthesis, which is overstimulated in cancer cells, makes this proposal attractive to improve and develop new approaches and strategies for cancer treatments. Indeed, the proposal has developed and improved new methods and innovative technologies to uncover new factors involved in genome stability allow us to improve in the diagnosis and prognosis, opening the possibility of more personalized medicine.
The overall objective of this action has been to assess rDNA damage and the ensuing genomic instability in human cells exposed to insults such as radiation, chemotherapy drugs, replication and transcription stress, ribosome biogenesis stress, and oncogenes, identify and functionally characterize signalling and repair factors that guard nucleolar integrity and function, and investigate how tumour cells may evade such control of nucleolar (replication) stress. To achieve these goals, we have employed innovative cellular models, molecular genetic, cell biology, and imaging technologies and functional assays. The expected results are providing novel insights into genome integrity maintenance and cellular stress responses and may inspire the design of future strategies to treat or even prevent cancer.
Unfortunately, during this active period, the current COVID-10 pandemia has impacted our society, our lives and also in our project execution due to the continuous outbreak in Denmark and strict restrictions in the research centre environment. To solve this situation, we have depth in some previous results obtained before COVID-19 outbreak, and we get promising results that they will publish soon, hopefully.