Mutations in DNA have a profound impact on a range of biological processes, including evolution, ageing, and disease. DNA mutation rates result from replication errors, various sources of damage, and the activity of counteracting repair pathways. Experimental and medical data indicate important links between transcription and mutation: transcription causes DNA damage and is coupled to DNA repair. However, the molecular aspects of these links and the extent to which they shape mutation rates remain poorly understood. To address this question, our consortium is performing large-scale mutation-accumulation experiments in dedicated microfluidic devices (developed in F. MALLOGGI team, CEA/Iramis) on genetically engineered mutant strains of the yeast Saccharomyces cerevisiae. This organism is indeed a very relevant model, given the conservation of transcription and DNA repair with multicellular eukaryotes, its short generation time, and its genetic tractability.

The work of Mariyam SAHO covers the main steps of the bioinfomatic analysis of mutation accumulation data. This starts with the bioinformatic processing of the raw sequencing data to establish the lists of mutations in mutation-accumulation lines needed to estimate mutation rates.