Our genome is constantly exposed to various types of DNA damage, both endogenous and exogenous. It has been estimated that the DNA in every cell of our body suffers thousands of DNA lesions per day, which, if left unattended, can lead to mutations or cell death. Luckily, our cells have evolved a variety of mechanisms to counteract deleterious effects of DNA damage, and if intact, these mechanisms are normally sufficient to sustain genome stability. Yet, not everyone is fortunate to inherit fully operational DNA damage response mechanisms and to date quite a number of genetic diseases are known to be linked to the defects in specific components of various DNA damage response pathways. Such diseases are readily associated with cancer, neurodegeneration, immunodeficiency or developmental abnormalities.
Our lab is utilising biochemical and cell-based assays to study mammalian DNA damage response pathways, which should lead to better understanding of the mechanisms underlying human disease and provide a basis for development of new therapies. We are particularly interested in pathways and protein functions regulated by poly(ADP-ribosyl)ation. Poly(ADP-ribosyl)ation is a posttranslational protein modification employed in regulation of DNA repair, chromatin structure, mitosis, transcription and apoptosis. Poly(ADP-ribose) is synthesised by PARP family of enzymes, which use NAD as a substrate. The recent development of potent specific PARP inhibitors provides powerful tools to study pathways regulated by poly(ADP-ribose), as well as provides one of the most promising class of drugs for cancer treatment.