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. doi: 10.1074/jbc.M608356200. Epub 2006 Nov 1.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Fanconi Anemia Complementation Group F Protein / chemistry*
  • Humans
  • Mitomycin / pharmacology*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Signal Transduction
  • Transcription Factors / metabolism
  • Ubiquitin / chemistry


  • CAND1 protein, human
  • FANCF protein, human
  • Fanconi Anemia Complementation Group F Protein
  • Transcription Factors
  • Ubiquitin
  • Mitomycin

Associated data

  • PDB/2IQC