The accurate replication and transmission of genetic material is of fundamental importance for cellular homeostasis and organism viability. Yet, cells are continually exposed to environmental and endogenous genotoxic agents that threaten DNA integrity. To protect their genomic stability, cells mount a complex network of DNA damage response pathways that activate cell cycle checkpoints, coordinate DNA repair, regulate gene expression and, if necessary, induce apoptosis. Indeed, DNA damage signalling and repair is a powerful barrier to tumourigenesis, and defects in these pathways promote cell proliferation and genomic instability in pre-malignant lesions. Genomic instability is also a hallmark of ageing. As such, the accumulation of DNA damage promotes not only the normal ageing process but is also linked to pre-mature ageing syndromes and to the onset of age-associated neurodegenerative diseases.
The overarching question of our research programme is how cells detect and repair DNA damage to safeguard their genetic information. In particular, we are interested in the regulatory mechanisms underlying DNA recombination and RNA metabolism at global sites of DNA damage, at telomeres and at distressed replication forks. [Find out more]