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BRCA1-independent ubiquitination of FANCD2.

Monoubiquitination of the FANCD2 protein is a key step in the Fanconi anemia (FA) tumor suppressor pathway, coinciding with this molecule's accumulation at sites of genome damage. Strong circumstantial evidence points to a requirement for the BRCA1 gene product in this step. Here, we show that the purified BRCA1/BARD1 complex, together with E1 and UbcH5a, is sufficient to reconstitute the monoubiquitination of FANCD2 in vitro. Although siRNA-mediated knockdown of BRCA1 in human cells results in defective targeting of FANCD2 to sites of DNA damage, it does not lead to a defect in FANCD2 ubiquitination. Furthermore, ablation of the RING finger domains of either BRCA1 or BARD1 in the chicken B cell line DT40 also leaves FANCD2 modification intact. Consequently, while BRCA1 affects the accumulation of FANCD2 at sites of DNA damage, BRCA1/BARD1 E3 ligase activity is not essential for the monoubiquitination of FANCD2.

Pubmed ID: 12887909


  • Vandenberg CJ
  • Gergely F
  • Ong CY
  • Pace P
  • Mallery DL
  • Hiom K
  • Patel KJ


Molecular cell

Publication Data

July 30, 2003

Associated Grants


Mesh Terms

  • Animals
  • BRCA1 Protein
  • Carrier Proteins
  • Cell-Free System
  • DNA Damage
  • Fanconi Anemia
  • Fanconi Anemia Complementation Group D2 Protein
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Humans
  • Iron-Binding Proteins
  • Ligases
  • Mutation
  • Nuclear Proteins
  • Protein Structure, Tertiary
  • RNA, Small Interfering
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligases