FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway

Blood. 2012 Apr 5;119(14):3285-94. doi: 10.1182/blood-2011-10-385963. Epub 2012 Feb 17.

Abstract

Fanconi anemia (FA) nuclear core complex is a multiprotein complex required for the functional integrity of the FA-BRCA pathway regulating DNA repair. This pathway is inactivated in FA, a devastating genetic disease, which leads to hematologic defects and cancer in patients. Here we report the isolation and characterization of a novel 20-kDa FANCA-associated protein (FAAP20). We show that FAAP20 is an integral component of the FA nuclear core complex. We identify a region on FANCA that physically interacts with FAAP20, and show that FANCA regulates stability of this protein. FAAP20 contains a conserved ubiquitin-binding zinc-finger domain (UBZ), and binds K-63-linked ubiquitin chains in vitro. The FAAP20-UBZ domain is not required for interaction with FANCA, but is required for DNA-damage-induced chromatin loading of FANCA and the functional integrity of the FA pathway. These findings reveal critical roles for FAAP20 in the FA-BRCA pathway of DNA damage repair and genome maintenance.

Publication types

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

MeSH terms

  • Cells, Cultured
  • Chromatin / metabolism
  • DNA Damage
  • DNA Repair*
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / metabolism*
  • Fanconi Anemia Complementation Group A Protein / chemistry
  • Fanconi Anemia Complementation Group A Protein / metabolism
  • Fanconi Anemia Complementation Group Proteins / chemistry
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Fanconi Anemia Complementation Group Proteins / metabolism*
  • Humans
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Stability
  • Signal Transduction*
  • Ubiquitin / metabolism*
  • Zinc Fingers

Substances

  • Chromatin
  • FAAP20 protein, human
  • Fanconi Anemia Complementation Group A Protein
  • Fanconi Anemia Complementation Group Proteins
  • Ubiquitin