Líffræðifélag Íslands
Líffræðiráðstefnan 2015
Erindi/veggspjald / Talk/poster V77
Þorkell Guðjónsson(1), Claudia Lukas(2), Jiri Lukas(2) and Stefán Sigurðsson(1)
1. Lífefna- og sameindalíffræðistofu, Lífvísindasetri Læknagarðs HÍ, 2. Novo Nordisk Foundation Center of Protein Research, University of Copenhagen, Denmark.
Kynnir / Presenter: Þorkell Guðjónsson
Tengiliður / Corresponding author: Þorkell Guðjónsson (thgud@hi.is)
Genomic instability is a characteristic of most cancers, believed to arise because of the inability of cells to deal with damaged DNA. To prevent genomic instability, cells possess a complex network of processes collectively called the DNA damage response (DDR). Individuals with inherited DDR defects, such as mutations in ATM, BRCA1 or BRCA2, are strongly associated with high cancer risk. To fully understand the molecular details of this important pathway identifying novel DDR regulators is essential. In a screen for novel genomic caretakers, we identified ubiquitin specific peptidase like 1 (USPL1). RNAi techniques were used to silence the expression of USPL1.USPL1 knockdown cells showed strong signs of genomic instability, including spontaneous DNA damage and abnormal nuclear morphology. When challenged with DNA damaging agents, USPL1 knockdown cells failed to efficiently repair broken DNA, and displayed hypersensitivity to PARP inhibition. Our preliminary results suggest that USPL1 might be important for the stability of the BRCA2 protein. In this project we identify USPL1, a protein with poorly understood functions, as a guardian of genomic stability. Our findings suggest that USPL1 plays a potential role in the regulation of DNA repair. Our future goal is to characterize the functional relationship between USPL1 and key DNA repair proteins in detail.