Alan D. D'Andrea, MD
Alvan T. and Viola D. Fuller American Cancer Society Professor of Radiation Oncology, Department of Radiation Oncology, Harvard Medical School
Scientific Director, Molecular Diagnostics Laboratory, Dana-Farber Cancer Institute
DF/HCC Program AffiliationLung CancerBreast Cancer
Fanconi Anema (FA) is an autosomal recessive disease characterized by progressive bone marrow failure and cancer susceptibility. Cells from patients with FA are hypersensitive to DNA-damaging agents, and the molecular defect is presumably one of DNA repair. FA has at least eight complementation groups (A-H), and three FA genes, corresponding to complementation groups A, C, and G have been cloned. We have recently demonstrated that the FANCA, FANCC, and FANCG proteins bind and form a nuclear complex, although the function of this complex remains unknown. More recently, we have demonstrated that the FANCA protein is phosphorylated and that its phosphorylation correlates with FANCC and FANCG binding and nuclear accumulation. Interestingly, other (non-A, C, G) FA cells are defective in FANCA phosphorylation, FA protein binding, and nuclear accumulation of the complex, suggesting that other FA gene products also regulate this pathway. Disruption of the pathway leads to chromosome instability and leukemia. On-going projects include the identification and cloining of other proteins in the FA complex and the biochemical assessment of the function of the nuclear FA complex.
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