The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder

Annu Rev Biophys. 2014:43:257-78. doi: 10.1146/annurev-biophys-051013-022737.


Mutations in any of at least sixteen FANC genes (FANCA-Q) cause Fanconi anemia, a disorder characterized by sensitivity to DNA interstrand crosslinking agents. The clinical features of cytopenia, developmental defects, and tumor predisposition are similar in each group, suggesting that the gene products participate in a common pathway. The Fanconi anemia DNA repair pathway consists of an anchor complex that recognizes damage caused by interstrand crosslinks, a multisubunit ubiquitin ligase that monoubiquitinates two substrates, and several downstream repair proteins including nucleases and homologous recombination enzymes. We review progress in the use of structural and biochemical approaches to understanding how each FANC protein functions in this pathway.

Keywords: DNA repair; Fanconi anemia; interstrand crosslink; structural biology; ubiquitin ligase.

Publication types

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

MeSH terms

  • Animals
  • DNA Damage
  • DNA Repair*
  • Fanconi Anemia / metabolism*
  • Fanconi Anemia Complementation Group A Protein / chemistry
  • Fanconi Anemia Complementation Group A Protein / metabolism
  • Humans
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Ubiquitin / genetics


  • Fanconi Anemia Complementation Group A Protein
  • Nuclear Proteins
  • Ubiquitin