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| | ==Architecture and DNA recognition elements of the Fanconi anemia FANCM- FAAP24 complex== | | ==Architecture and DNA recognition elements of the Fanconi anemia FANCM- FAAP24 complex== |
| - | <StructureSection load='4bxo' size='340' side='right' caption='[[4bxo]], [[Resolution|resolution]] 2.15Å' scene=''> | + | <StructureSection load='4bxo' size='340' side='right'caption='[[4bxo]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4bxo]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BXO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4bxo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BXO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bxo RCSB], [http://www.ebi.ac.uk/pdbsum/4bxo PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4bxo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bxo OCA], [https://pdbe.org/4bxo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bxo RCSB], [https://www.ebi.ac.uk/pdbsum/4bxo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bxo ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN]] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/FANCM_HUMAN FANCM_HUMAN] Fanconi anemia. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FANCM_HUMAN 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.<ref>PMID:16116422</ref> <ref>PMID:16116434</ref> [REFERENCE:7][REFERENCE:8] [[http://www.uniprot.org/uniprot/FAP24_HUMAN 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. | + | [https://www.uniprot.org/uniprot/FANCM_HUMAN 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.<ref>PMID:16116422</ref> <ref>PMID:16116434</ref> [REFERENCE:7][REFERENCE:8] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4bxo" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: RNA helicase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bowles, M]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Costa, A]] | + | [[Category: Bowles M]] |
| - | [[Category: Coulthard, R]] | + | [[Category: Costa A]] |
| - | [[Category: Deans, A]] | + | [[Category: Coulthard R]] |
| - | [[Category: McDonald, N]] | + | [[Category: Deans A]] |
| - | [[Category: Purkiss, A]] | + | [[Category: McDonald N]] |
| - | [[Category: Swuec, P]] | + | [[Category: Purkiss A]] |
| - | [[Category: West, S]] | + | [[Category: Swuec P]] |
| - | [[Category: Dna binding]]
| + | [[Category: West S]] |
| - | [[Category: Hydrolase-dna complex]]
| + | |
| - | [[Category: Pseudo-nuclease]]
| + | |
| 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]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005 Sep;37(9):958-63. Epub 2005 Aug 21. PMID:16116422 doi:ng1626
- ↑ Mosedale G, Niedzwiedz W, Alpi A, Perrina F, Pereira-Leal JB, Johnson M, Langevin F, Pace P, Patel KJ. The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway. Nat Struct Mol Biol. 2005 Sep;12(9):763-71. Epub 2005 Aug 21. PMID:16116434 doi:10.1038/nsmb981
- ↑ Coulthard R, Deans AJ, Swuec P, Bowles M, Costa A, West SC, McDonald NQ. Architecture and DNA Recognition Elements of the Fanconi Anemia FANCM-FAAP24 Complex. Structure. 2013 Aug 6. pii: S0969-2126(13)00255-4. doi:, 10.1016/j.str.2013.07.006. PMID:23932590 doi:10.1016/j.str.2013.07.006
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