Background information
Fanconi anemia (FA) is an autosomal recessive disorder characterized by bone marrow failure, birth defects and chromosomal instability. At the cellular level, FA is characterized by spontaneous chromosomal breakage and a unique hypersensitivity to DNA cross-linking agents. At least eight complementation groups (A-G) have been identified and six FA genes (for subtypes A, C, D2, E, F and G) have been cloned. The FA proteins lack sequence homologies or motifs that could point to a molecular function. The cellular accumulation of FA proteins, including FANCA and FANCG, is subject to regulation by TNF alpha signaling. Phosphorylation of FANC (Fanconi anemia complementation group) proteins is thought to be important for the function of the FA pathway. FANCA, also known as FACA and FANCH, associates with the Brm-related gene 1 (BRG1) product, a subunit of the SWI/SNF complex which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA is mainly expressed in lymphoid tissues, testis and ovary. The amino-terminal region of the FANCA protein is required for FANCG binding, FANCC binding, nuclear localization and functional activity of the complex. The human FANCA gene maps to chromosome 16q24.3 and encodes a 1,455 amino acid protein.
