Features of chromosomal aberrations, hypersensitivity to DNA crosslinking 
agents, and predisposition to malignancy have suggested a fundamental anomaly of 
DNA repair in Fanconi anemia. The function of the recently isolated FACC 
(Fanconi anemia group C complementing) gene for a subset of this disorder is not 
yet known. The notion that FACC plays a direct role in DNA repair would predict 
that the polypeptide should reside in the nucleus. In this study, a polyclonal 
antiserum raised against FACC was used to determine the subcellular location of 
the polypeptide. Immunofluorescence and subcellular fractionation studies of 
human cell lines as well as COS-7 cells transiently expressing human FACC showed 
that the protein was localized primarily to the cytoplasm under steady-state 
conditions, transit through the cell cycle, and exposure to crosslinking or 
cytotoxic agents. However, placement of a nuclear localization signal from the 
simian virus 40 large tumor antigen at the amino terminus of FACC directed the 
hybrid protein to the nuclei of transfected COS-7 cells. These observations 
suggest an indirect role for FACC in regulating DNA repair in this group of 
Fanconi anemia.