Fanconi anemia (FA) is a rare genetic disorder characterized by aplastic anemia, 
cancer/leukemia susceptibility and cellular hypersensitivity to DNA crosslinking 
agents, such as cisplatin. To date, 12 FA gene products have been identified, 
which cooperate in a common DNA damage-activated signaling pathway regulating 
DNA repair (the FA pathway). Eight FA proteins form a nuclear complex harboring 
E3 ubiquitin ligase activity (the FA core complex) that, in response to DNA 
damage, mediates the monoubiquitylation of the FA protein FANCD2. 
Monoubiquitylated FANCD2 colocalizes in nuclear foci with proteins involved in 
DNA repair, including BRCA1, FANCD1/BRCA2, FANCN/PALB2 and RAD51. All these 
factors are required for cellular resistance to DNA crosslinking agents. The 
inactivation of the FA pathway has also been observed in a wide variety of human 
cancers and is implicated in the sensitivity of cancer cells to DNA crosslinking 
agents. Drugs that inhibit the FA pathway may be useful chemosensitizers in the 
treatment of cancer. Publication history: Republished from Current BioData's 
Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).