Fanconi anemia-associated nuclease 1 (FAN1)

Fanconi anemia-associated nuclease 1 (FAN1) is a structure-specific DNA endonuclease and exonuclease that plays a central role in DNA interstrand crosslink repair. It is recruited to sites of DNA damage via interaction with the monoubiquitinated FANCI-FANCD2 complex, primarily in response to crosslinking agents such as mitomycin C and cisplatin. FAN1 possesses 5′-flap endonuclease and 5′ to 3′ exonuclease activities, and helps resolve DNA interstrand crosslinks to maintain genome integrity. Germline and acquired mutations of FAN1 are implicated in Fanconi anemia (a disorder of bone marrow failure and cancer predisposition), hereditary colorectal cancer, karyomegalic interstitial nephritis, and possibly neuropsychiatric disease. FAN1 is considered a tumor suppressor and is being studied for its role in modulating sensitivity to chemotherapeutics that induce DNA crosslinking.

Other names

FANCD2/FANCI-associated nuclease 1KIAA1018Fan1

Drugs (like mitomycin C and cisplatin) induce DNA crosslinks that require FAN1 for cellular resistance and repair. Loss or inhibition of FAN1 increases cellular sensitivity to DNA crosslinking agents, leading to cell death or genomic instability.