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Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.

Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Although six FA genes (for subtypes A, C, D2, E, F, and G) have been cloned, their relationship to DNA repair remains unknown. In the current study, we show that a nuclear complex containing the FANCA, FANCC, FANCF, and FANCG proteins is required for the activation of the FANCD2 protein to a monoubiquitinated isoform. In normal (non-FA) cells, FANCD2 is monoubiquitinated in response to DNA damage and is targeted to nuclear foci (dots). Activated FANCD2 protein colocalizes with the breast cancer susceptibility protein, BRCA1, in ionizing radiation-induced foci and in synaptonemal complexes of meiotic chromosomes. The FANCD2 protein, therefore, provides the missing link between the FA protein complex and the cellular BRCA1 repair machinery. Disruption of this pathway results in the cellular and clinical phenotype common to all FA subtypes.

Pubmed ID: 11239454


  • Garcia-Higuera I
  • Taniguchi T
  • Ganesan S
  • Meyn MS
  • Timmers C
  • Hejna J
  • Grompe M
  • D'Andrea AD


Molecular cell

Publication Data

February 12, 2001

Associated Grants

  • Agency: NHLBI NIH HHS, Id: P01HL54785-04
  • Agency: NIDDK NIH HHS, Id: R01DK43889-09
  • Agency: NHLBI NIH HHS, Id: R01HL52725-04

Mesh Terms

  • Active Transport, Cell Nucleus
  • Animals
  • BRCA1 Protein
  • Cell Cycle Proteins
  • Cell Line
  • Cell Survival
  • DNA Damage
  • DNA-Binding Proteins
  • Fanconi Anemia
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group Proteins
  • Fluorescent Antibody Technique
  • Genetic Complementation Test
  • Humans
  • Macromolecular Substances
  • Male
  • Meiosis
  • Mice
  • Mitomycin
  • Nuclear Proteins
  • Protein Binding
  • Proteins
  • Radiation, Ionizing
  • Spermatocytes
  • Synaptonemal Complex
  • Ubiquitins
  • Ultraviolet Rays