Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex.

Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure, congenital abnormalities, cancer susceptibility, and a marked cellular hypersensitivity to DNA interstrand cross-linking agents, which correlates with a defect in ability to repair this type of damage. We have previously identified an approximately 230-kDa protein present in a ...
nuclear protein complex in normal human lymphoblastoid cells that is involved in repair of DNA interstrand cross-links and shows reduced levels in FA-A cell nuclei. The FANCA gene appears to play a role in the stability or expression of this protein. We now show that p230 is a well known structural protein, human alpha spectrin II (alphaSpIISigma*), and that levels of alphaSpIISigma* are not only significantly reduced in FA-A cells but also in FA-B, FA-C and FA-D cells (i.e. in all FA cell lines tested), suggesting a role for these FA proteins in the stability or expression of alphaSpIISigma*. These studies also show that alphaSpIISigma* forms a complex in the nucleus with the FANCA and FANCC proteins. alphaSpIISigma* may thus act as a scaffold to align or enhance interactions between FA proteins and proteins involved in DNA repair. These results suggest that FA represents a disorder in which there is a deficiency in alphaSpIISigma*.
Mesh Terms:
Blotting, Western, Cell Cycle Proteins, Cell Line, DNA Repair, DNA-Binding Proteins, Fanconi Anemia, Fanconi Anemia Complementation Group A Protein, Fanconi Anemia Complementation Group C Protein, Fanconi Anemia Complementation Group Proteins, Hela Cells, Humans, Nuclear Proteins, Peptides, Precipitin Tests, Protein Binding, Proteins, Spectrin, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
J. Biol. Chem.
Date: Nov. 12, 1999
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