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Crystal structure of the C-terminal segment of FANCM in complex with FAAP24Crystal structure of the C-terminal segment of FANCM in complex with FAAP24
Structural highlights
Disease[FANCM_HUMAN] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry. Function[FANCM_HUMAN] ATPase required for FANCD2 ubiquitination, a key reaction in DNA repair. Binds to ssDNA but not to dsDNA. Recruited to forks stalled by DNA interstrand cross-links, and required for cellular resistance to such lesions.[1] [2] [REFERENCE:7][REFERENCE:8] [FAP24_HUMAN] Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA. Publication Abstract from PubMedFanconi 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. Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair.,Yang H, Zhang T, Tao Y, Wang F, Tong L, Ding J Nucleic Acids Res. 2013 Sep 3. PMID:24003026[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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