Fanconi anemia complementation group I protein (FANCI)

Fanconi anemia complementation group I protein (FANCI) is a nuclear protein encoded by the FANCI gene in humans. It is a core component of the Fanconi anemia (FA) DNA repair pathway, especially vital for the repair of DNA interstrand crosslinks. FANCI functions as a heterodimer with its partner FANCD2; both proteins undergo monoubiquitination by the FA core complex (notably via the FANCL E3 ubiquitin ligase), an essential modification for DNA repair. The monoubiquitinated FANCI:FANCD2 complex localizes to and coats damaged DNA sites, protecting stalled replication forks and promoting DNA repair. FANCI is also involved in ribosomal RNA processing and protein synthesis regulation in the nucleolus and participates in meiotic recombination. Mutations in FANCI cause Fanconi anemia, a syndrome marked by congenital abnormalities, bone marrow failure, and increased cancer risk[2][7][9]. FANCI’s dysfunction is associated with chromosomal instability and hypersensitivity to DNA crosslinking agents. Although drugs directly targeting FANCI are not in clinical use, pathway inhibition (e.g., with MLN4924 or similar agents) reveals synthetic lethality networks that are being explored as potential therapeutic strategies in cancer[2].

Other names

KIAA1794FA-associated protein IFanconi anemia, complementation group I

Inhibition of the Fanconi anemia pathway (e.g., synthetic lethality for drugs like MLN4924 inhibiting NEDD8-activating enzyme and thus indirectly impacting FANCI function)[2]