FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA

Mutat Res. 2009 Jul 31;668(1-2):20-6. doi: 10.1016/j.mrfmmm.2009.04.002. Epub 2009 Apr 18.

Abstract

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA-crosslinking agents. Eight FA proteins (FANCA, -B, -C, -E, -F, -G, -L and -M) and three non-FA proteins (FAAP100, FAAP24 and HES1) form the FA nuclear core complex that is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. The other three FA proteins, FANCD1/BRCA2, FANCJ/BACH1/BRIP1 and FANCN/PALB2, act in parallel or downstream of the FANCD2-FANCI dimer. Despite the isolation and characterization of several FA proteins, the mechanism by which these proteins protect cells from DNA interstrand crosslinking agents has been unclear. This is because a majority of the FA proteins lack any recognizable functional domains that can provide insight into their function. The recently discovered FANCM (Hef) and FANCJ (BRIP1/BACH1) proteins contain helicase domains, providing potential insight into the role of FA proteins in DNA repair. FANCM with its partner, FAAP24, and FANCJ bind and metabolize a variety of DNA substrates. In this review, we focus on the discovery, structure, and function of the FANCM-FAAP24 and FANCJ proteins.

Publication types

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

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / chemistry
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • DNA / metabolism
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism*
  • DNA Repair*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Drug Discovery
  • Fanconi Anemia / metabolism*
  • Fanconi Anemia Complementation Group Proteins / chemistry
  • Fanconi Anemia Complementation Group Proteins / metabolism*
  • Humans
  • Structure-Activity Relationship

Substances

  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • FAAP24 protein, human
  • Fanconi Anemia Complementation Group Proteins
  • DNA
  • FANCM protein, human
  • DNA Helicases