DNA Damage and Genome Regulation

Our research focuses on understanding the mechanisms behind genome rearrangements caused by DNA double-strand breaks (DSBs). These rearrangements can have both positive and negative effects, contributing to genetic diversity and disease development, particularly cancer. While we have knowledge about externally induced DNA fragile sites, the factors influencing spontaneous DSBs in different genomic regions and the underlying mechanisms remain unknown.

In collaboration with our partners, we use advanced genomics techniques to analyse DNA breaks at the nucleotide level and investigate chromatin interactions using chromosome conformation capture methods. In doing so, we aim to uncover the sources of intrinsic DNA fragility and how they contribute to tissue-specific oncogenesis. We will focus on the role of non-canonical DNA structures such as R-loops and G-quadruplexes as well as on incomplete topoisomerase actions and their potential interference with replication and transcription. Using machine learning models, we will build predictive models to identify intrinsic DNA fragility in the human genome and identify the most influential features and their interdependencies. With our project, we aim to identify why certain regions of the genome are more prone to breakage and thus gain valuable insights into the emergence of recurrent genome rearrangements and their link to oncogenesis.