Identification of FAAP24, a Fanconi Anemia Core Complex Protein that Interacts with FANCM

• DOI: 10.1016/j.molcel.2007.01.003
• Publication Date: 2007-02-09T12:06:04Z
• Authors: Alberto Ciccia; Chen Ling; Rachel Coulthard; Zhijiang Yan; Yutong Xue; Amom Ruhikanta Me...; El Houari Laghmani; Hans Joenje; Neil McDonald; Johan P. de Winter; Weidong Wang; Stephen C. West
• Keywords: DNA Replication; 0303 health sciences; DNA Repair; Sequence Homology, Amino Acid; Ubiquitin; Molecular Sequence Data; DNA Helicases; Cell Biology; Fanconi Anemia Complementation Group Proteins; Protein Structure, Tertiary; DNA-Binding Proteins; 03 medical and health sciences; Multigene Family; Two-Hybrid System Techniques; Humans; Amino Acid Sequence; Molecular Biology; Sequence Alignment; DNA Damage

The Fanconi anemia (FA) core complex plays a crucial role in a DNA damage response network with BRCA1 and BRCA2. How this complex interacts with damaged DNA is unknown, as only the FA core protein FANCM (the homolog of an archaeal helicase/nuclease known as HEF) exhibits DNA binding activity. Here, we describe the identification of FAAP24, a protein that targets FANCM to structures that mimic intermediates formed during the replication/repair of damaged DNA. FAAP24 shares homology with the XPF family of flap/fork endonucleases, associates with the C-terminal region of FANCM, and is a component of the FA core complex. FAAP24 is required for normal levels of FANCD2 monoubiquitylation following DNA damage. Depletion of FAAP24 by siRNA results in cellular hypersensitivity to DNA crosslinking agents and chromosomal instability. Our data indicate that the FANCM/FAAP24 complex may play a key role in recruitment of the FA core complex to damaged DNA.