PREDOC2023 (CM)- DNA damage tolerance and genome stability

The goal of our group is to contribute to the understanding of how genome integrity is maintained during chromosome replication, especially under genotoxic or replicative stress conditions. This is a biological problem of interest in basic and biomedical research, given that genomic instability, frequently caused by DNA damage, is a hallmark of premature ageing, developmental abnormalities, neurological disorders or cancer. The work will be mainly focused on the study of the regulation of the different mechanisms involved in DNA damage tolerance (DDT), which are highly conserved in eukaryotes, and how this regulation may be important for their function in the maintenance of genome stability. The methodology to be used will combine genetics, molecular biology, cell biology and biochemistry techniques, and thus will allow the prospective PhD student to acquire broad experimental and theoretical competence in Biosciences. The budding yeast Saccharomyces cerevisiae will be used as an eukaryotic working model. The research plan will include the study of: (1) the subcellular relocalization of DDT proteins under conditions of DNA damage or replicative stress; (2) posttranslational modifications of DDT proteins in a normal cell cycle and in response to genotoxic and replicative stress; (3) the modulation of DDT mechanisms by other pathways; (4) the crosstalk between the different branches of DDT and between DDT and other processes.