Genome Stability - PhD and honours Projects - Regulation of DNA damage signaling by the tumour suppressor FANCM

Regulation of DNA damage signaling by the tumour suppressor FANCM

Project Type

Honours

Summary

FANCM is deficient in a subset of patients with Fanconi anaemia, a genetic disorder that results in progressive depletion of blood stem cells, and a 700-fold increase in leukaemia risk. FANCM is also mutated in sporadic breast cancers. Previous work in the lab has shown that the FANCM protein plays an important role in recognising damaged DNA and activating a pathway that is required for active DNA repair (Deans and West, Molecular Cell, 2009). The proposed research involves exploring the mechanism by which FANCM stimulates this pathway, leading to the avoidance of cancer causing mutations. A combination of approaches will be used such as cell culture with patient cell lines, studies on chemotherapy toxicity, protein interaction and expression studies and analysis of recombinant human FANCM using state-of-the-art insect cell expression systems. The outcome of this research will be of importance to treatment of Fanconi anaemia and sporadic cancers.