The role of RNA binding protein TIRR in kidney cancer

About the project

About the Project Eukaryotic cells employ a carefully coordinated network of signalling and repair proteins to resolve DNA damage, known as the DNA damage response (DDR). The most lethal form of DNA damage is double-stranded breaks (DSBs). Two key pathways in DSB repair are homologous recombination (HR) and non-homologous end joining (NHEJ). In HR, resection occurs at the break to expose ssDNA, allowing for homologous DNA to associate and act as a template for error-free repair. Contrastingly, NHEJ is error prone, involving digestion and ligation of the break, permitting the introduction of insertions and deletions. Tudor Interacting Repair Regulator (TIRR), sits at the interface of HR and NHEJ. TIRR is well-established as an inhibitor of 53BP1 (1-4), an integral factor in promoting NHEJ. Upon the formation of DSBs, TIRR and 53BP1 dissociate, allowing recognition of chromatin (1). Interestingly, TIRR is a versatile mRNA binding protein (2,5,6). TIRR is also amplified across various cancer cell lines. We have found that kidney cancer cells are highly sensitive to TIRR depletion, which makes it an excellent clinical target. In this project, we aim to understand the molecular mechanism behind TIRR sensitivity in kidney cancer. We will employ array of molecular techniques to investigate the role of TIRR in normal and kidney cancer cells. Data obtained from this project will have translational potential, which will be explored further.

Research areas