Positional cloning of a novel fanconi anemia gene, FANCD2

Fanconi anemia (FA) is a genetic disease with birth defects, bone marrow fa ilure, and cancer susceptibility. To date, genes for five of the seven know n complementation groups have been cloned. Complementation group D is heter ogeneous, consisting of two distinct genes, FANCD1 and FANCD2. Here we repo rt the positional cloning of FANCD2. The gene consists of 44 exons, encodes a novel 1451 amino acid nuclear protein, and has two protein isoforms. Sim ilar to other FA proteins, the FANCD2 protein has no known functional domai ns, but unlike other known FA genes, FANCD2 is highly conserved in A. thali ana, C. elegans, and Drosophila. Retroviral transduction of the cloned FANC D2 cDNA into FA-D2 cells resulted in functional complementation of MMC sens itivity.