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Evolved Replication Systems for Epigenetics

Final Report Summary - EVOEPIGEN (Evolved Replication Systems for Epigenetics)

DNA methylation is the most abundant DNA modification in vertebrates. Alterations of DNA methylation play a crucial role in the onset of diseases (e.g. cancer, neurodevelopmental and metabolic disorders, autoimmune diseases). Many DNA methylation-based biomarkers have been evaluated and the analysis of epigenetic alterations is a promising and emerging tool for disease diagnostics, prognostics, and prediction of response to therapies. In future, this will allow to adapt therapies to a person (‘personalized medicine’) which will increase the chance for successful treatments, minimizing side-effects of chemotherapy and administration of ineffective drugs and thus prevent follow-up problems associated with these events. This means that cost-effective but robust means that allow the analysis of DNA methylation-based biomarkers are of urgent need.
The aim of this ERC project was to overcome the barriers that prohibit using DNA methylation profiling in broad clinical applications for diagnostics, prognostics, and prediction of drug response. We are developing approaches that are superior to known techniques by superseding the troublesome and time-consuming conversion of DNA by bisulfite treatment or any other manipulation prior to analysis.
Within this project, we provided the basis for the development of artificial replication systems, which allow the significantly simplified analysis of DNA methylation sites by direct usage of DNA samples without prior chemical treatment. Thereby, we have combined chemical, biochemical, and molecular biological tools. Our approaches are focused on the development of new methylation-specific PCR and DNA methylation sequencing approaches. We also could solve the structural basis for DNA polymerases that interact with non-canonical substrates.