1. Cloning and analysis of the mouse Fanconi anemia group a cDNA and an overlapping penta zinc finger cDNA
- Author
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Jasmine C. Wong, Koenraad Norga, Hagop Youssoufian, Frank A.E. Kruyt, Noa Alon, Manuel Buchwald, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
Male ,Gene Expression ,CHROMOSOMAL INSTABILITY ,GENE FAA ,Polymerase Chain Reaction ,Mice ,Fanconi anemia ,hemic and lymphatic diseases ,TRANSCRIPTION ,Cloning, Molecular ,Peptide sequence ,Cells, Cultured ,Genomic organization ,Zinc finger ,Genetics ,Fanconi Anemia Complementation Group A Protein ,NUCLEAR ACCUMULATION ,Reverse Transcriptase Polymerase Chain Reaction ,Zinc Fingers ,EXON ,DNA-Binding Proteins ,Phenotype ,MESSENGER-RNA ,Chromosomes, Human, Pair 8 ,Adult ,GROUP-C CDNA ,congenital, hereditary, and neonatal diseases and abnormalities ,DNA, Complementary ,Molecular Sequence Data ,Biology ,Complementary DNA ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Gene ,DNA Primers ,Cloning ,COMPLEX ,Base Sequence ,Sequence Homology, Amino Acid ,MUTATIONS ,Genetic Complementation Test ,Proteins ,nutritional and metabolic diseases ,GROUP-A PROTEIN ,medicine.disease ,Blotting, Northern ,Molecular biology ,FANCA ,Mice, Inbred C57BL ,Fanconi Anemia - Abstract
Despite the cloning of four disease-associated genes for Fanconi anemia (FA), the molecular pathogenesis of FA remains largely unknown. To study FA complementation group A using the mouse as a mode I system, we cloned and characterized the mouse homolog of the human FANCA cDNA, The mouse cDNA (Fanca) encodes a 161-kDa protein that shares 65% amino acid sequence identity with human FANCA. Fanca is located at the distal region of mouse chromosome 8 and has a ubiquitous pattern of expression in embryonic and adult tissues. Expression of the mouse DNA in human FA-A cells restores the cellular drug sensitivity to normal levels. Thus, the expression pattern, protein structure, chromosomal location, and function of FANCA are conserved in the mouse. We also isolated a novel zinc finger protein, Zfp276, which has five C2H2 domains. Interestingly, Zfp276 is situated in the Fanca locus, and the 3'UTR of its cDNA overlaps with the last four exons of Fanca in a tail-to-tail manner. Zfp276 is expressed in the same tissues as Fanca, but does not complement the mitomycin C (MMC)-sensitive phenotype of FA-A cells. The overlapping genomic organization between Zfp276 and Fanca may have relevance to the disease phenotype of FA. (C) 2000 Academic Press.
- Published
- 2000