Grant: Operating Grant

Our genome is organized into long pieces of DNA, called chromosomes. Cancer is caused by the accumulation of changes in DNA (mutations) that result in the activation of "oncogenes" and the inactivation of "tumor suppressors". Some changes involve one or a few bases of DNA, whereas genomic rearrangements involve the gain or the loss of whole chromosomes or sections of chromosomes as well as rearrangements between two chromosomes. Cells have developed mechanisms to detect and repair changes in DNA. In the context of tumour development and progression, mutations are believed to accumulate owing to compromised DNA repair functions. Yet, to replicate their DNA and proliferate, cancer cells need DNA repair mechanisms, perhaps even more than do normal cells because the cancer phenotype causes multiple stresses to DNA. Moreover, efficient DNA repair pathway can help cancer cells resist therapeutic treatments that target DNA, like radiotherapy and most chemotherapeutic agents. In this project, we will investigate a protein domain called Cut repeat that is present in a number of proteins and help accelerate the DNA repair pathway that fixes damaged bases in DNA. There are two ways by which our work can ultimately be helpful to cancer patients. First, we will generate unique tools -reagents and methods- that can serve as predictive indicators that will be used in diagnostic laboratories to predict the response of specific tumors to particular treatments and therefore help the patient and the clinician decide what is the best course of action. Secondly, our work will identify proteins and enzymatic reactions that can be controlled with a drug. We will thus have identified suitable targets for future therapeutic strategies.