4bxo | pdb_00004bxo

Architecture and DNA recognition elements of the Fanconi anemia FANCM- FAAP24 complex

spinqualitylabelsall models 4bxo, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bxo is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Activity: RNA helicase, with EC number 3.6.4.13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. [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 PubMed Fanconi anemia (FA) is a disorder associated with a failure in DNA repair. FANCM (defective in FA complementation group M) and its partner FAAP24 target other FA proteins to sites of DNA damage. FANCM-FAAP24 is related to XPF/MUS81 endonucleases but lacks endonucleolytic activity. We report a structure of an FANCM C-terminal fragment (FANCMCTD) bound to FAAP24 and DNA. This S-shaped structure reveals the FANCM (HhH)2 domain is buried, whereas the FAAP24 (HhH)2 domain engages DNA. We identify a second DNA contact and a metal center within the FANCM pseudo-nuclease domain and demonstrate that mutations in either region impair double-stranded DNA binding in vitro and FANCM-FAAP24 function in vivo. We show the FANCM translocase domain lies in proximity to FANCMCTD by electron microscopy and that binding fork DNA structures stimulate its ATPase activity. This suggests a tracking model for FANCM-FAAP24 until an encounter with a stalled replication fork triggers ATPase-mediated fork remodeling. Architecture and DNA Recognition Elements of the Fanconi Anemia FANCM-FAAP24 Complex.,Coulthard R, Deans AJ, Swuec P, Bowles M, Costa A, West SC, McDonald NQ Structure. 2013 Aug 6. pii: S0969-2126(13)00255-4. doi:, 10.1016/j.str.2013.07.006. PMID:23932590 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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