Required for maintenance of chromosomal stability. Involved in the repair of DNA double-strand breaks by homologous recombination and in the repair of DNA cross-links. Participates in S phase and G2 phase checkpoint activation upon DNA damage. Promotes FANCD2 ubiquitination and recruitment to DNA repair sites.
Involvement in disease
Defects in FANCI are a cause of Fanconi anemia complementation group I (FANCI) [MIM:609053]. It is a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
The C-terminal 30 residues are probably required for function in DNA repair.
Monoubiquitinated on Lys-523 during S phase and upon genotoxic stress. Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the FANCA-FANCB-FANCC-FANCE-FANCF-FANCG-FANCM complex. Ubiquitination is required for binding to chromatin, DNA repair, and normal cell cycle progression. Phosphorylated in response to DNA damage by ATM and/or ATR.
Nucleus. Concentrates in nuclear foci upon genotoxic stress.
Detection of Human KIAA1794 by Immunoprecipitation in Whole cell lysate from HeLa cells (1 mg for IP, 20% of IP loaded) using ab74332 at 3 µg/mg for IP (Lane 1) and at 1 µg/ml for subsequent WB detection. Lane 2 represents IgG control IP.
Luebben SW et al. A concomitant loss of dormant origins and FANCC exacerbates genome instability by impairing DNA replication fork progression. Nucleic Acids Res42:5605-15 (2014).
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