Exposure to environmental factors, including sunlight, ionizing radiation and chemical reagents, constantly challenges the integrity of our genetic information (i.e DNA). To ensure that our DNA is faithfully transmitted and to prevent the development of cancer, cells have evolved a complex network to detect, signal and ultimately repair DNA damage, which is coupled to an arrest in cell proliferation. It is still poorly understood how DNA damage signaling/repair and cell cycle arrest are coordinated but recent evidence suggests the implication of the cell cycle protein cyclin D1 (D1). Tight regulation of D1 protein level is critical as overexpression of D1 can predispose to the development of cancer. The major goal of my project is to characterize the mechanisms regulating D1 levels and its biological functions in cell cycle progression and DNA repair. In particular, I will define the interaction of D1 with the deubiquitinating enzyme USP11, which could protect D1 from degradation and be a potential target for the development of anti-cancer drugs. We will verify whether modulation of USP11 levels impacts the stability and the endogenous level of D1 as well as cell cycle progression and DNA repair. We will also investigate the clinical importance of D1-USP11 interaction and screen for drugs that could affect D1 level and cancer progression. This study will give insight into the mechanisms coordinating DNA signaling/repair and cell cycle progression and could reveal how a defect in these mechanisms can promote cancer progression. Ultimately, our study could provide with potential drug target to treat patients affected by D1-overexpressing cancers.