The role of FANCM gene in inherited breast cancer

Summary 1 in 10 breast cancers are due to inheritance of a predisposing gene. In half of these cases, the inherited gene mutation is in the well characterised BRCA1 or BRCA2 genes. The normal function of BRCA1 and BRCA2 is in DNA repair, to suppress cancer by removing the damage to DNA that is caused by carcinogens. Over the last few years, many other DNA repair genes have been linked with familial breast cancer, including the FANCM gene. Our lab studies the mechanism of DNA repair by the FANCM protein using cell-based and protein chemistry-based approaches. This project will test the breast-cancer associated FANCM mutations identified in a screen of 11,000 women with a history of breast cancer, in a set of assays so that we may determine why they might predispose to breast cancer.

Project Details

1 in 10 breast cancers are due to inheritance of a predisposing gene. In half of these cases, the inherited gene mutation is in the well characterised BRCA1 or BRCA2 genes. The normal function of BRCA1 and BRCA2 is in DNA repair, to suppress cancer by removing the damage to DNA that is caused by carcinogens. Over the last few years, many other DNA repair genes have been linked with familial breast cancer, including the FANCM gene.

Our lab studies the mechanism of DNA repair by the FANCM protein using cell-based and protein chemistry-based approaches.  This project will test the breast-cancer associated FANCM mutations identified in a screen of 11,000 women with a history of breast cancer, in a set of assays so that we may determine why they might predispose to breast cancer. A combination of approaches will be used such as studies on chemotherapy toxicity, generation of CRISPR knockout cell lines, and purification and functional testing of recombinant human FANCM using state-of-the-art protein expression systems. There will also be the opportunity to work with patient samples and clinical implementation of findings. This project will be part of a larger Cancer Australia-funded study into the role of DNA repair in cancer initiation and chemotherapy.