A rare
genetic disease,
Fanconi anemia (FA), now attracts broader attention from
cancer biologists and basic researchers in the DNA repair and
ubiquitin biology fields as well as from hematologists. FA is a
chromosome instability syndrome characterized by childhood-onset
aplastic anemia,
cancer or
leukemia susceptibility, and cellular
hypersensitivity to
DNA crosslinking agents. Identification of 11 genes for FA has led to progress in the molecular understanding of this disease. FA
proteins, including a
ubiquitin ligase (FANCL), a monoubiquitinated
protein (FANCD2), a helicase (FANCJ/BACH1/BRIP1), and a breast/
ovarian cancer susceptibility
protein (
FANCD1/BRCA2), appear to cooperate in a pathway leading to the recognition and repair of damaged
DNA. Molecular interactions among FA
proteins and responsible
proteins for other
chromosome instability syndromes (BLM, NBS1, MRE11, ATM, and ATR) have also been found. Furthermore, inactivation of FA genes has been observed in a wide variety of human
cancers in the general population. These findings have broad implications for predicting the sensitivity and resistance of
tumors to widely used anticancer
DNA crosslinking agents (
cisplatin,
mitomycin C, and
melphalan). Here, we summarize recent progress in the molecular biology of FA and discuss roles of the FA
proteins in DNA repair and
cancer biology.