Reactome: A Curated Pathway Database

Fanconi Anemia pathway (R-HSA-419524)

Species Homo sapiens

Summation

Fanconi anemia (FA) is a genetic disease of genome instability characterized by congenital skeletal defects, aplastic anemia, susceptibility to leukemias, and cellular sensitivity to DNA damaging agents. Patients with FA have been categorized into at least 13 complementation groups (FA-A, -B, -C, -D1, -D2, -E, -F, -G, -I, -J, -L, -M, and -N). These complementation groups correspond to the genes FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCJ/BRIP1, FANCL, FANCM, and FANCN/PALB2. Although the functions of most of these proteins are mostly unknown, eight of them, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, and FANCM products together with AAP24 and FAAP100 form a nuclear complex termed the FA core complex. The core complex is essential for FANCD2 and FANCI monoubiquitination after DNA damage. FANCD2 and FANCI are mutually dependent on one another for their respective monoubiquitination. After DNA damage and during S phase, FANCD2 localizes to chromatin, forming foci that overlap those containing proteins involved in homologous recombination, such as BRCA1 and RAD51. The FA pathway is regulated by the deubiquitination of FANCD2 and the phosphorylation FANCD2 and FANCI. The USP1/UAF1 complex is responsible for deubiquitination of FANCD2 and negatively regulates the FA pathway (Cohn et al., 2007) ATR and ATM dependent phosphorylation of FANCD2 promotes the monoubiquitination of FANCD2 stimulating the FA pathway (Cohn and D'Andrea, 2008; Wang, 2007).

Locations in the PathwayBrowser
Additional Information
Compartment nucleoplasm