Fanconi anemia (FA), a recessive syndrome with both autosomal and X-linked 
inheritance, features diverse clinical symptoms, such as progressive bone marrow 
failure, hypersensitivity to DNA cross-linking agents, chromosomal instability 
and susceptibility to cancer. At least 12 genetic subtypes have been described 
(FA-A, B, C, D1, D2, E, F, G, I, J, L, M) and all except FA-I have been linked 
to a distinct gene. Most FA proteins form a complex that activates the FANCD2 
protein via monoubiquitination, while FANCJ and FANCD1/BRCA2 function downstream 
of this step. The FA proteins typically lack functional domains, except for 
FANCJ/BRIP1 and FANCM, which are DNA helicases, and FANCL, which is probably an 
E3 ubiquitin conjugating enzyme. Based on the hypersensitivity to cross-linking 
agents, the FA proteins are thought to function in the repair of DNA interstrand 
cross-links, which block the progression of DNA replication forks. Here we 
present a hypothetical model, which not only describes the assembly of the FA 
pathway, but also positions this pathway in the broader context of DNA 
cross-link repair. Finally, the possible role for the FA pathway, in particular 
FANCF and FANCB, in the origin of sporadic cancer is discussed.