New pharmacological targets in Fanconi Anemia

The Fanconi Anemia syndrome is a rare hereditary disease caused by mutations in at least 13 genes. These genes code for proteins that interact with each other and eventually regulate the FANCD2 protein activity. Being the last ring of this chain of events, it is likely that this protein is the one responsible of the pathology in all the Fanconi Anemia cases. We have demonstrated that this protein is involved in preventing error prone repair of DNA lesions. The Fanconi Anemia patients show a large spectrum of symptoms (among which predisposition to cancer and poor fertility) explainable on the whole by the incapacity of properly repairing DNA damage. The pathology is so complex in its manifestations that the diagnosis and the therapy are often delayed and therefore ineffectual. If a cell is unable to accurately repair DNA, it accumulates mutations and is potentially dangerous to the whole organism, therefore its elimination can be more opportune than its survival. We have a detailed knowledge of the battery of genes involved in DNA repair and cell death in one of the most useful model organisms for these kinds of studies: the nematode C. elegans that has already been shown useful for the understanding of human pathologies (in fact the Nobel Prize for Medicine 2002 and 2006 have been assigned because of researches in this nematode). Our recent success in understanding the role of FANCD2 protein in accurate DNA repair and of the deleterious effects of its absence or malfunctioning and the long-term experience in the biochemical study of proteins involved in DNA metabolism can now lead to the identification of new drug targets for therapy in particular to prevent/delay the onset of cancer in these patients that is still their most frequent cause of death.