InterPro domain: IPR026848

Fanconi anemia (FA) is a human disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. The FA complex repairs the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. It is required for the monoubiquitylation of FANCD2 and FANCI heterodimer. The FA core complex consists of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FANCT (UBET2), FAAP100 and FAAP24 [ 1 , 2 ].

FANCL is an ubiquitin ligase that mediates monoubiquitination of FANCD2, a key step in the repair of interstrand DNA crosslinks (ICLs) in the Fanconi anemia (FA) pathway [ 3 , 4 ]. In humans, defects in FANCL are the cause of Fanconi anemia complementation group L (FANCL). FANCL is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair [ 5 , 6 ].

1. DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway. Cell Commun. Signal 15, 41
2. A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol. Cell 37, 865-78
3. UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Mol. Cell. Biol. 27, 8421-30
4. DNA robustly stimulates FANCD2 monoubiquitylation in the complex with FANCI. Nucleic Acids Res. 40, 4553-61
5. A novel ubiquitin ligase is deficient in Fanconi anemia. Nat. Genet. 35, 165-70
6. X-linked inheritance of Fanconi anemia complementation group B. Nat. Genet. 36, 1219-24