Fanconi anaemia and the repair of Watson and Crick DNA crosslinks

Nature. 2013 Jan 17;493(7432):356-63. doi: 10.1038/nature11863.

Abstract

The function of Fanconi anaemia proteins is to maintain genomic stability. Their main role is in the repair of DNA interstrand crosslinks, which, by covalently binding the Watson and the Crick strands of DNA, impede replication and transcription. Inappropriate repair of interstrand crosslinks causes genomic instability, leading to cancer; conversely, the toxicity of crosslinking agents makes them a powerful chemotherapeutic. Fanconi anaemia proteins can promote stem-cell function, prevent tumorigenesis, stabilize replication forks and inhibit inaccurate repair. Recent advances have identified endogenous aldehydes as possible culprits of DNA damage that may induce the phenotypes seen in patients with Fanconi anaemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism*
  • DNA Repair*
  • Ethanol / metabolism
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / metabolism*
  • Fanconi Anemia / pathology
  • Fanconi Anemia Complementation Group Proteins / metabolism*
  • Humans
  • Stem Cells / metabolism

Substances

  • Fanconi Anemia Complementation Group Proteins
  • Ethanol
  • DNA