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FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway.

The EMBO journal | Apr 18, 2007

http://www.ncbi.nlm.nih.gov/pubmed/17396147

The Fanconi anemia (FA) core complex plays a central role in the DNA damage response network involving breast cancer susceptibility gene products, BRCA1 and BRCA2. The complex consists of eight FA proteins, including a ubiquitin ligase (FANCL) and a DNA translocase (FANCM), and is essential for monoubiquitination of FANCD2 in response to DNA damage. Here, we report a novel component of this complex, termed FAAP100, which is essential for the stability of the core complex and directly interacts with FANCB and FANCL to form a stable subcomplex. Formation of this subcomplex protects each component from proteolytic degradation and also allows their coregulation by FANCA and FANCM during nuclear localization. Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability. Our study identifies FAAP100 as a new critical component of the FA-BRCA DNA damage response network.

Pubmed ID: 17396147 RIS Download

Mesh terms: BRCA1 Protein | BRCA2 Protein | DNA Damage | DNA Helicases | DNA-Binding Proteins | Fanconi Anemia Complementation Group L Protein | HeLa Cells | Humans | Models, Molecular | Multiprotein Complexes | Oligonucleotides | RNA Interference

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Associated grants

  • Agency: NCI NIH HHS, Id: CA112775
  • Agency: NCI NIH HHS, Id: R01CA82678
  • Agency: NHLBI NIH HHS, Id: R37HL32987

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