4reb
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4reb]] is a 5 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=4REB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4REB FirstGlance]. <br> | <table><tr><td colspan='2'>[[4reb]] is a 5 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=4REB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4REB FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SM:SAMARIUM+(III)+ION'>SM</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]] 4.2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SM:SAMARIUM+(III)+ION'>SM</scene></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=4reb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4reb OCA], [https://pdbe.org/4reb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4reb RCSB], [https://www.ebi.ac.uk/pdbsum/4reb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4reb ProSAT]</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=4reb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4reb OCA], [https://pdbe.org/4reb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4reb RCSB], [https://www.ebi.ac.uk/pdbsum/4reb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4reb ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/FAN1_HUMAN FAN1_HUMAN] Nuclease required for maintenance of chromosomal stability. Plays a key role in DNA repair of DNA interstrand cross-links (ICL) by being recruited to sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL-induced DNA breaks by being required for efficient homologous recombination, possibly in the resolution of homologous recombination intermediates. Not involved in DNA double-strand breaks resection. Has both endonuclease activity toward 5'-flaps and 5'-exonuclease activity: may act in concert with the 3'-flap-specific enzymes to unhook the ICL by cleaving the lagging-strand template.<ref>PMID:20603015</ref> <ref>PMID:20603016</ref> <ref>PMID:20603073</ref> <ref>PMID:20671156</ref> | [https://www.uniprot.org/uniprot/FAN1_HUMAN FAN1_HUMAN] Nuclease required for maintenance of chromosomal stability. Plays a key role in DNA repair of DNA interstrand cross-links (ICL) by being recruited to sites of DNA damage by monoubiquitinated FANCD2. Specifically involved in repair of ICL-induced DNA breaks by being required for efficient homologous recombination, possibly in the resolution of homologous recombination intermediates. Not involved in DNA double-strand breaks resection. Has both endonuclease activity toward 5'-flaps and 5'-exonuclease activity: may act in concert with the 3'-flap-specific enzymes to unhook the ICL by cleaving the lagging-strand template.<ref>PMID:20603015</ref> <ref>PMID:20603016</ref> <ref>PMID:20603073</ref> <ref>PMID:20671156</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5' flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA and unwind a 5' flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1. | ||
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| - | Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer.,Zhao Q, Xue X, Longerich S, Sung P, Xiong Y Nat Commun. 2014 Dec 11;5:5726. doi: 10.1038/ncomms6726. PMID:25500724<ref>PMID:25500724</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4reb" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Structural Insights into 5' Flap DNA Unwinding and Incision by the Human FAN1 Dimer
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Categories: Homo sapiens | Large Structures | Synthetic construct | Longerich S | Sung P | Xiong Y | Xue X | Zhao Q
