Mutations in DNA have large-ranging consequences, from evolution to aging and diseases. Dysfunctions in DNA repair and transcription, and mutagen exposures can increase the rate of mutations. It remains poorly understood how the complex relationship between transcription and DNA repair influences mutational processes. Recently, we discovered that Mediator, a crucial coactivator of transcription conserved in all eukaryotes, have a novel function in transcription-coupled repair. The aim of this interdisciplinary project is to improve our understanding of the mutational processes by deciphering how Mediator implication in transcription-coupled repair influences transcription-associated mutagenesis. To precisely dissect the molecular mechanisms involved in mutagenesis, we will use our innovative approach based on microfluidics, genomics and computational analysis for mutation accumulation in budding yeast combined with mutagen exposure and transfer the acquired knowledge to human cells.