Grant: Operating Grant

All organisms have evolved mechanisms that allow the maintenance of genomic integrity. The consequences of damaged DNA, and especially double-strand breaks, may be disastrous and lead to cancer if left unrepaired. All organisms can suffer DNA damage, during normal cellular processes or as a consequence of DNA damaging agents such as UV and ionizing radiation. Conversely, treatment of cancer cells with chemotherapy and radiotherapy aims at damaging the DNA of cancer cells to kill them specifically. In that case, it is an advantage to inhibit DNA repair. The present project aims at understanding how cells detect and repair DNA double-strand breaks. Particularly, we want to understand how poly(ADP-ribose), a molecule which is synthesized at sites of damaged DNA, orchestrates the detection and repair of broken DNA. Specifically, we will analyze how poly(ADP-ribose) polymerases affect the pathways by which double-strand breaks are repaired. Because some studies have shown the usefulness of inhibiting poly(ADP-ribose) synthesis in killing breast, ovarian and pancreatic cancer cells, understanding the interplay between poly(ADP-ribose) and proteins involved in DNA damage repair is critical to design better cancer therapy regimes and to improve clinical outcome.