Dragana Ahel

Mechanisms of Genome Stability

The maintenance of a complete and undamaged genome is critical for survival. Because DNA is continuously exposed to genotoxic stress, cells have evolved mechanisms that are specialized for correcting different types of DNA damage. These mechanisms play essential roles in the maintenance of genome integrity and their deficiencies have been associated with ageing and cancer.

The mechanisms that maintain genome stability show amazing complexity and our laboratory is interested in discovering unknown aspects of their function. We are particularly interested in a large family of helicase-like proteins called SNF2 ATPases, characterised by the presence of a specific ATPase domain. SNF2 ATPases are widespread among eukaryotes, but are also represented in bacteria and archaea. They are a functionally heterogeneous family of proteins and regulate diverse nuclear functions, including transcription, DNA replication, DNA repair and recombination. Moreover, many SNF2 family members have been linked to human disease and cancer. Their role in human pathologies is documented by several developmental disorders associated with mutations in SNF2 ATPase genes. In addition, SNF2 ATPases have emerged as contributing factors in a variety of human cancers. Different SNF2 ATPases play different roles in cancer: whereas some act as tumour suppressors, others have oncogenic functions.

We are also interested in identifying novel factors involved in the maintenance of genome stability outside of the SNF2 ATPase family. We use a multidisciplinary approach to study these factors at a biochemical, cellular, and physiological level. Our aim is to provide a detailed picture of their function and improve our understanding of fundamental cellular mechanisms that impact on genome stability and play a role in human disease.