FIG. 9.

Schematic model of molecular interactions of the FANCA, FANCG, and FANCC proteins. Based on available data, at least two regions of the FANCA polypeptide are required for the FANCA-FANCG-FANCC interaction. First, the amino-terminal region of the FANCA protein, which includes the bipartite NLS region, is required for interaction with the FANCG protein. Second, a region near the carboxy terminus of FANCA is required for the FANCC interaction. Patient-derived point mutations in this region disrupt the FANCC interaction. The FANCC interaction is a weak or regulated interaction, requiring FANCA/FANCG binding and the products of other FA genes (44). The region of FANCG required for FANCA binding is not known. The region of FANCC required for FANCA binding may be the carboxy terminus of FANCC. This region is highly conserved among human, murine, and bovine FANCC proteins. Also, an FA-C patient-derived point mutation [FANCC(L554P)] ablates FANCA binding (21).