RNA-binding proteins (RBP) play critical roles in stress responses like DNA-damage through interactions with elements in functionally related RNAs, termed regulons. One of the most cytotoxic forms of DNA-damage are DNA double strand breaks (DSB), that can lead to mutagenic events and when improperly repaired to cell death. This proposed project focuses on the dynamics of the global RBP network (mRNA-interactome) and RNA-regulons of mouse fibroblasts (NIH-3T3) cells in response to genotoxic stress. The “RNA-regulon” model implies that RBPs control functionally related mRNAs via cis-regulatory elements in these RNAs. Using mRNA-interactome capture and high-resolution quantitative proteomics, I will comprehensively identify mRNA-binding proteins involved in immediate DNA-repair and cell death responses to genotoxic stress. By employing deep sequencing and crosslink immunoprecipitation approaches, I will highlight the controlled RNA-networks and their influence on cell survival. Taken together, this project aims to address key questions of the role for RBPs in the DNA-damage response at different stages and the identification of their RNA-regulons. Furthermore, it opens new perspectives in posttranscriptional regulation after the cells exposure to genotoxic stress. The innovative nature of this interdisciplinary project involves European collaborators, which creates excellent inter-European-networking. The development of a novel research area will showcase the cutting-edge research performed in the ERA thus directly contribute to the European Work Programme by enhancing the attractiveness of Europe for third country and European top-scientists.