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4rea

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Revision as of 08:49, 11 August 2016

A Nuclease DNA complex

Structural highlights

4rea is a 5 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4reb, 4rec
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[FAN1_HUMAN] Karyomegalic interstitial nephritis. The disease is caused by mutations affecting the gene represented in this entry.

Function

[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.^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ MacKay C, Declais AC, Lundin C, Agostinho A, Deans AJ, MacArtney TJ, Hofmann K, Gartner A, West SC, Helleday T, Lilley DM, Rouse J. Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2. Cell. 2010 Jul 9;142(1):65-76. doi: 10.1016/j.cell.2010.06.021. PMID:20603015 doi:http://dx.doi.org/10.1016/j.cell.2010.06.021
↑ Kratz K, Schopf B, Kaden S, Sendoel A, Eberhard R, Lademann C, Cannavo E, Sartori AA, Hengartner MO, Jiricny J. Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell. 2010 Jul 9;142(1):77-88. doi: 10.1016/j.cell.2010.06.022. PMID:20603016 doi:http://dx.doi.org/10.1016/j.cell.2010.06.022
↑ Smogorzewska A, Desetty R, Saito TT, Schlabach M, Lach FP, Sowa ME, Clark AB, Kunkel TA, Harper JW, Colaiacovo MP, Elledge SJ. A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair. Mol Cell. 2010 Jul 9;39(1):36-47. doi: 10.1016/j.molcel.2010.06.023. PMID:20603073 doi:http://dx.doi.org/10.1016/j.molcel.2010.06.023
↑ Liu T, Ghosal G, Yuan J, Chen J, Huang J. FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair. Science. 2010 Aug 6;329(5992):693-6. doi: 10.1126/science.1192656. Epub 2010 Jul , 29. PMID:20671156 doi:http://dx.doi.org/10.1126/science.1192656
↑ Zhao Q, Xue X, Longerich S, Sung P, Xiong Y. Structural insights into 5' flap DNA unwinding and incision by the human FAN1 dimer. Nat Commun. 2014 Dec 11;5:5726. doi: 10.1038/ncomms6726. PMID:25500724 doi:http://dx.doi.org/10.1038/ncomms6726

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rea"

@@ Line 1: / Line 1: @@
 ==A Nuclease DNA complex==
 <StructureSection load='4rea' size='340' side='right' caption='[[4rea]], [[Resolution|resolution]] 3.81&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4rea]] is a 5 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4REA FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4reb|4reb]], [[4rec|4rec]]</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=4rea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rea OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rea RCSB], [http://www.ebi.ac.uk/pdbsum/4rea PDBsum]</span></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=4rea FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rea OCA], [http://pdbe.org/4rea PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rea RCSB], [http://www.ebi.ac.uk/pdbsum/4rea PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rea ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 18: / Line 19: @@
 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>
 == References ==
 <references/>

4rea

From Proteopedia

Revision as of 08:49, 11 August 2016

A Nuclease DNA complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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