Open AccessLocalization of Fanconi anemia C protein to the cytoplasm of mammalian cells.
Author(s) -
Hagop Youssoufian
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.17.7975
Subject(s) - fanconi anemia , biology , transfection , microbiology and biotechnology , dna repair , cytoplasm , dna , cell culture , genetics
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.