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==Human FAN1 nuclease==
==Human FAN1 nuclease==
<StructureSection load='4rid' size='340' side='right' caption='[[4rid]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
<StructureSection load='4rid' size='340' side='right'caption='[[4rid]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4rid]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RID OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RID FirstGlance]. <br>
<table><tr><td colspan='2'>[[4rid]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RID OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RID FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ri8|4ri8]], [[4ri9|4ri9]], [[4ria|4ria]], [[4rib|4rib]], [[4ric|4ric]]</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]] 3.3&#8491;</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=4rid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rid OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rid RCSB], [http://www.ebi.ac.uk/pdbsum/4rid 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=4rid FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rid OCA], [https://pdbe.org/4rid PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rid RCSB], [https://www.ebi.ac.uk/pdbsum/4rid PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rid ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/FAN1_HUMAN FAN1_HUMAN]] Karyomegalic interstitial nephritis. The disease is caused by mutations affecting the gene represented in this entry.  
[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 ==
== Function ==
[[http://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 ==
DNA interstrand cross-links (ICLs) are highly toxic lesions associated with cancer and degenerative diseases. ICLs can be repaired by the Fanconi anemia (FA) pathway and through FA-independent processes involving the FAN1 nuclease. In this work, FAN1-DNA crystal structures and biochemical data reveal that human FAN1 cleaves DNA successively at every third nucleotide. In vitro, this exonuclease mechanism allows FAN1 to excise an ICL from one strand through flanking incisions. DNA access requires a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3' flap, suggesting that FAN1 action is coupled to DNA synthesis or recombination. FAN1's mechanism of ICL excision is well suited for processing other localized DNA adducts as well.
 
DNA repair. Mechanism of DNA interstrand cross-link processing by repair nuclease FAN1.,Wang R, Persky NS, Yoo B, Ouerfelli O, Smogorzewska A, Elledge SJ, Pavletich NP Science. 2014 Nov 28;346(6213):1127-30. doi: 10.1126/science.1258973. PMID:25430771<ref>PMID:25430771</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Pavletich, N P]]
[[Category: Homo sapiens]]
[[Category: Wang, R]]
[[Category: Large Structures]]
[[Category: Hydrolase]]
[[Category: Pavletich NP]]
[[Category: Nuclease]]
[[Category: Wang R]]

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