View source for 4rea


==A Nuclease DNA complex==
<StructureSection load='4rea' size='340' side='right'caption='[[4rea]], [[Resolution|resolution]] 3.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rea]] 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=4REA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4REA FirstGlance]. <br>
</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=4rea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rea OCA], [https://pdbe.org/4rea PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rea RCSB], [https://www.ebi.ac.uk/pdbsum/4rea PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rea ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FAN1_HUMAN FAN1_HUMAN] Karyomegalic interstitial nephritis. The disease is caused by mutations affecting the gene represented in this entry.
== 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> 
<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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4rea" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Longerich S]]
[[Category: Sung P]]
[[Category: Xiong Y]]
[[Category: Xue X]]
[[Category: Zhao Q]]