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

Irene Garcia-Higuera, Toshiyasu Taniguchi, Shridar Ganesan, M. Stephen Meyn, Cynthia Timmers, James Hejna, Markus Grompe, Alan D. D'Andrea

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)249-262
Number of pages14
JournalMolecular Cell
Volume7
Issue number2
DOIs
Publication statusPublished - 2001

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ASJC Scopus subject areas

  • Molecular Biology

Cite this

Garcia-Higuera, I., Taniguchi, T., Ganesan, S., Meyn, M. S., Timmers, C., Hejna, J., ... D'Andrea, A. D. (2001). Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Molecular Cell, 7(2), 249-262. https://doi.org/10.1016/S1097-2765(01)00173-3