Research units - Genome Stability

Genome Stability

The Genome Stabiliity Unit is the newest addition to St Vincent’s Institute. Our lab focuses on the mechanisms cells use to protect themselves from cancer-causing mutations.

Research Overview

We study familial cancer syndromes that cause predisposition to breast/ovarian cancer, leukaemias and other solid tumours. These families inherit a defect in the ability to maintain genome stability – their cells accumulate mutations at a faster rate, and thus cancer occurs earlier in life with a higher probability. This mechanism of genome stability is intricate and involves a number of signaling and DNA repair pathways. We are beginning to reconstitute these pathways biochemically using recombinant proteins and synthetic DNA molecules to understand how they function and how they could be targeted with small molecule inhibitors. We also study the chemotherapeutic sensitivity of human tumour cell lines that have defects in maintaining genome stability. 

Research Themes

The structure and function of DNA repair signalling proteins

Novel inhibitors of DNA repair as chemotherapy sensitisers in breast cancer

The role of FANCM in the repair of DNA interstrand crosslinks

Post-translational modification of DNA repair proteins

Honours and PhD Projects

Regulation of DNA damage signaling by the tumour suppressor FANCM

Inhibition of the Bloom’s syndrome pathway as a mechanism of chemotherapy

Staff

Dr Andrew Deans
Sylvie van Twest

Publication Highlights

    1. Deans, AJ and West, SC. DNA interstrand crosslink repair and cancer. Nature Reviews Cancer 2011 11:467-480
    2. MacKay C, Déclais, AC, Lundin C, Agostinho A, Deans, AJ, MacArtney, TJ, Hofmann, K, Gartner, A, West, SC, Helleday, T, Lilley DMJ and Rouse, J. Identification of KIAA1018/FAN1, a DNA Repair Nuclease Recruited to DNA Damage by Monoubiquitinated FANCD2. Cell 2010 142:65-76
    3. Deans, AJ and West, SC. FANCM connects the genome instability disorders Bloom’s Syndrome and FanconiAnemia. Molecular Cell 2009 36, 943-953
    4. Spurdle AB, Deans AJ, Duffy D, Goldgar DE, Chen X, Beesley J; kConFaB, Easton DF, Antoniou AC, Peock, S, Cook M; EMBRACE Study Collaborators, Nathanson KL, Domchek SM, Macarthur GA, Chenevix-Trench G. No evidence that CDKN1B (p27) polymorphisms modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 2009 115:307-13
    5. Collis SJ, Ciccia A, Deans AJ, Horejsí Z, Martin JS, Maslen SL, Skehel JM, Elledge SJ, West SC, Boulton SJ. FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anaemia core complex. Molecular Cell 2008 32:313-24.
    6. Deans AJ, Khanna KK, McNees CJ, Mercurio C, Heierhorst J, McArthur GA. Cyclin-dependent kinase 2 functions in normal DNA repair and is a therapeutic target in BRCA1-deficient cancers. Cancer Research 2006 66:8219-26
    7. Deans AJ, Simpson KJ, Trivett M, Brown MA, McArthur GA. Brca1 inactivation induces p27Kip1-dependent cell cycle arrest and delayed development in the mouse mammary gland. Oncogene. 2004 23:6136-45