- Honours or PhD
Uncontrolled cell proliferation, a hallmark of tumour cells, leads to high levels of replication-related lesions and double strand breaks (DSBs). As a survival strategy some cancers have elevated activity of the Homologous Recombination (HR) pathway, the main pathway repairing DSBs arising from replication stress, or promote other error-prone repair pathways capable of compensating defective HR. Thus, thorough understanding of the mechanisms by which cancer cells alleviate the ongoing replication stress and endogenous DNA lesions will unravel novel therapeutic targets and opportunities.
Rearranged L-myc fusion (RLF), an epigenetic modifier, is found to be amplified/gained in a significant proportion of ovarian (50%) and other cancers. A previous study has shown that that RLF interacts with components of DNA damage sensing complex, MRN, a tricomplex critical for HR pathway (Harten et al, 2015, BMC Biology). Using a murine-derived knockout cell model we have further established that RLF is required to modulate cellular replication stress. We will conduct further investigations using this established cell model to analyse the role of RLF in HR mediated DNA repair during replication stress and extrapolate it’s function in ovarian cancer tumourigenesis. Scholars will gain skills extensively in cell culture, molecular biology techniques including western blotting, immunofluoresence, immunoprecipitation and FACS.