Positional cloning of a novel Fanconi anemia gene, FANCD2.
Fanconi anemia (FA) is a genetic disease with birth defects, bone marrow failure, and cancer susceptibility. To date, genes for five of the seven known complementation groups have been cloned. Complementation group D is heterogeneous, consisting of two distinct genes, FANCD1 and FANCD2. Here we report the positional cloning of FANCD2. The gene consists of 44 exons, encodes a novel 1451 amino acid nuclear protein, and has two protein isoforms. Similar to other FA proteins, the FANCD2 protein has no known functional domains, but unlike other known FA genes, FANCD2 is highly conserved in A. thaliana, C. elegans, and Drosophila. Retroviral transduction of the cloned FANCD2 cDNA into FA-D2 cells resulted in functional complementation of MMC sensitivity.
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, OR 97201, USA.
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Timmers
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Taniguchi
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Hejna
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Reifsteck
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Lucas
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Bruun
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Thayer
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Cox
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Olson
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D'Andrea
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Moses
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Grompe
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D019457:Chromosome Breakage / Q000235:genetics; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D004852:Epoxy Compounds / Q000494:pharmacology; D005199:Fanconi Anemia / Q000235:genetics*; D052236:Fanconi Anemia Complementation Group D2 Protein; D005260:Female; D020869:Gene Expression Profiling; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016415:Sequence Alignment; D014161:Transduction, Genetic
D029721:Drosophila Proteins; D004852:Epoxy Compounds; C499905:FANCD2 protein, human; C499906:Fancd2 protein, Drosophila; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016685:Mitomycin; C007366:diepoxybutane