Fanconi anemia is an autosomal recessive syndrome characterized by diverse 
clinical symptoms, hypersensitivity to DNA crosslinking agents, chromosomal 
instability and susceptibility to cancer. Fanconi anemia has at least 11 
complementation groups (A, B, C, D1, D2, E, F, G, I, J, L); the genes mutated in 
8 of these have been identified. The gene BRCA2 was suggested to underlie 
complementation group B, but the evidence is inconclusive. Here we show that the 
protein defective in individuals with Fanconi anemia belonging to 
complementation group B is an essential component of the nuclear protein 'core 
complex' responsible for monoubiquitination of FANCD2, a key event in the 
DNA-damage response pathway associated with Fanconi anemia and BRCA. 
Unexpectedly, the gene encoding this protein, FANCB, is localized at Xp22.31 and 
subject to X-chromosome inactivation. X-linked inheritance has important 
consequences for genetic counseling of families with Fanconi anemia belonging to 
complementation group B. Its presence as a single active copy and essentiality 
for a functional Fanconi anemia-BRCA pathway make FANCB a potentially vulnerable 
component of the cellular machinery that maintains genomic integrity.