Fanconi anemia complementation group C protein (FANCC)

The Fanconi anemia complementation group C (FANCC) protein is a vital component of the Fanconi anemia (FA) core complex, which functions as an E3 ubiquitin ligase assembly necessary for the repair of DNA interstrand cross-links (ICLs) [1, 5, 10]. This pathway is primarily activated during the S-phase of the cell cycle when DNA replication forks are stalled by covalent bonds between DNA strands [5, 15]. FANCC facilitates the monoubiquitination of the FANCD2 and FANCI proteins, a critical signaling event that recruits downstream repair factors such as BRCA1 and BRCA2 to the site of damage [2, 5]. In addition to its nuclear role in maintaining genomic stability, FANCC exerts non-canonical functions in the cytoplasm, including the regulation of mitophagy, modulation of STAT1 signaling, and suppression of cytokine-induced apoptosis [8, 11]. Mutations in the FANCC gene lead to Fanconi anemia complementation group C, a condition characterized by progressive bone marrow failure, developmental anomalies, and a high risk of developing acute myeloid leukemia and various solid tumors [10, 16]. In clinical oncology, FANCC deficiency serves as a biomarker for synthetic lethality, making affected tumors highly sensitive to PARP inhibitors and DNA-damaging agents like cisplatin [6, 9, 12]. Emerging therapeutic strategies include gene editing to correct mutations in hematopoietic stem cells and translational read-through drugs like ataluren for patients with nonsense mutations [7, 13, 18].

Other names

FACFACCFA3Fanconi pancytopenia type 3 proteinFanconi anemia group C protein

Synthetic lethality (PARP inhibition in deficient cells), Translational read-through (Ataluren for nonsense mutations), Gene replacement/editing, DNA cross-linking (cytotoxicity in deficient cells)