Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair.
Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first ... crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair.
Mesh Terms:
Binding Sites, DNA, DNA Helicases, DNA Repair, DNA-Binding Proteins, HEK293 Cells, Humans, Models, Molecular, Protein Interaction Domains and Motifs
Binding Sites, DNA, DNA Helicases, DNA Repair, DNA-Binding Proteins, HEK293 Cells, Humans, Models, Molecular, Protein Interaction Domains and Motifs
Nucleic Acids Res.
Date: Dec. 01, 2013
PubMed ID: 24003026
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