Structural highlights
Disease
[FANCF_HUMAN] Defects in FANCF are the cause of Fanconi anemia complementation group F (FANCF) [MIM:603467]. 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.[1]
Function
[FANCF_HUMAN] DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability (By similarity).
Publication Abstract from PubMed
Fanconi anemia (FA) is a rare autosomal recessive and X-linked chromosomal instability disorder. At least eight FA proteins (FANCA, B, C, E, F, G, L, and M) form a nuclear core complex required for monoubiquitination of a downstream protein, FANCD2. The human FANCF protein reportedly functions as a molecular adaptor within the FA nuclear complex, bridging between the subcomplexes A:G and C:E. Our x-ray crystallographic studies of the C-terminal domain of FANCF reveal a helical repeat structure similar to the Cand1 regulator of the Cul1-Rbx1-Skp1-Fbox(Skp2) ubiquitin ligase complex. Two C-terminal loops of FANCF are essential for monoubiquitination of FANCD2 and normal cellular resistance to the DNA cross-linking agent mitomycin C. FANCF mutants bearing amino acid substitutions in this C-terminal surface fail to interact with other components of the FA complex, indicating that this surface is critical for the proper assembly of the FA core complex.
Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex.,Kowal P, Gurtan AM, Stuckert P, D'Andrea AD, Ellenberger T J Biol Chem. 2007 Jan 19;282(3):2047-55. Epub 2006 Nov 1. PMID:17082180[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ de Winter JP, Rooimans MA, van Der Weel L, van Berkel CG, Alon N, Bosnoyan-Collins L, de Groot J, Zhi Y, Waisfisz Q, Pronk JC, Arwert F, Mathew CG, Scheper RJ, Hoatlin ME, Buchwald M, Joenje H. The Fanconi anaemia gene FANCF encodes a novel protein with homology to ROM. Nat Genet. 2000 Jan;24(1):15-6. PMID:10615118 doi:10.1038/71626
- ↑ Kowal P, Gurtan AM, Stuckert P, D'Andrea AD, Ellenberger T. Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex. J Biol Chem. 2007 Jan 19;282(3):2047-55. Epub 2006 Nov 1. PMID:17082180 doi:M608356200
