Hématologie
MENUFanconi's anemia: from genes to function Volume 7, issue 6, Novembre - Décembre 2001
Figures
- Key words: Fanconi anemia, multiunit complex FANC, interaction FANC/BRAC1, apoptosis, oxidative damage, DNA repair.
- Page(s) : 410-7
- Published in: 2002
Fanconi anemia (FA) is a rare genetic disease demonstrating a complex phenotype including severe pancytopenia, a variety of developmental anomalies and a high predisposition to acute myeloblastic leukemia. FA cells are characterized by hypersensitivity to DNA cross-linking agents and by high frequencies of chromosomal aberrations, a property used for diagnosis. FA results from mutations in one of the eight genes FANCA, B, C, D1, D2, E, F and G. Six of these genes have been cloned and characterized. With the exception of FancD2 no homologies with known proteins have been reported. Fanc proteins form a nuclear multisubunit complex. Mutations in any of the FANC genes hampers the formation of a functional complex. A number of experimental observations including the recently demonstrated interaction of one of these proteins (FancD2) with the breast cancer associated BRCA1 protein strongly suggest a role of the complex in the recombinational repair of DNA double strand breaks. Moreover, at least the FancC protein, partially located in the cytoplasm, plays a role in interferon gamma and tumor necrosis alpha induced apoptosis. This protection of hematopoietic cells results from interference with the response to oxidative damage. Bone marrow transplantation is at the moment the major therapy in FA; the analysis of FANC proteins and a better understanding of their function(s) are likely to provide new therapeutic strategies.