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Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM

Alberto Ciccia1, Chen Ling, Rachel Coulthard

  • 1Cancer Research UK, London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK.

Molecular Cell
|February 10, 2007
PubMed

Insights

Researchers identified FAAP24, a protein that targets FANCM to DNA damage sites. This interaction is crucial for the Fanconi anemia (FA) core complex

Area of Science:

  • Molecular Biology
  • Genetics
  • DNA Repair

Background:

  • The Fanconi anemia (FA) core complex is vital for DNA damage response, interacting with BRCA1 and BRCA2.
  • The mechanism by which the FA core complex engages with damaged DNA remains unclear, with only FANCM showing DNA binding activity.

Purpose of the Study:

  • To identify proteins that facilitate the interaction of the FA core complex with damaged DNA.
  • To elucidate the role of novel protein partners in DNA damage response pathways.

Main Methods:

  • Protein identification and characterization.
  • Analysis of protein-protein interactions using co-immunoprecipitation.
  • siRNA-mediated gene silencing to assess cellular function.
  • Assessment of DNA crosslinking agent sensitivity and chromosomal stability.

Main Results:

  • FAAP24 was identified as a protein that targets FANCM to DNA structures mimicking replication/repair intermediates.
  • FAAP24 shares homology with XPF endonucleases, binds FANCM, and is part of the FA core complex.
  • FAAP24 is essential for FANCD2 monoubiquitylation and its depletion causes hypersensitivity to DNA crosslinking agents and chromosomal instability.

Conclusions:

  • The FANCM/FAAP24 complex is proposed to be key in recruiting the FA core complex to damaged DNA sites.
  • FAAP24 plays a critical role in maintaining genomic stability through its involvement in the FA pathway.

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