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

Mol Cell. 2001 Feb;7(2):249-62. doi: 10.1016/s1097-2765(01)00173-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • BRCA1 Protein
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • FANCC protein, human
  • Fancc protein, mouse
  • Fanconi Anemia Complementation Group C Protein
  • Fanconi Anemia Complementation Group Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • Proteins
  • Ubiquitins
  • Mitomycin