DNA Recombination, Replication and Genome Stability

During an average human life span, each individual copies several light-years of DNA to ensure organism development and tissue homeostasis. Flaws in the DNA replication process, known as replication stress, result in inaccurate chromosome duplication and subsequent mitotic abnormalities. Replication stress has emerged as a major source of genome instability contributing to genomic disorders, neurological diseases, aging and cancer.

The causes of replication stress are many and varied but ultimately result in stressed replication forks that are fragile DNA structures prone to chromosomal rearrangements. Our main research line is to investigate the spatial and temporal organization of molecular circuits that prevent stressed forks to be converted into pathological DNA structures and the inheritance of DNA lesions and epi-genetic changes to the progeny.

We combine genetics, genomics, cellular and molecular approaches that allow us to explore how recombination, repair and chromatin-based processes resolve replication stress within the sub-nuclear architecture of the genome. We make use of the yeast S. pombe and human cells to address those questions.