5iii

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==Crystal structure of the pre-catalytic ternary complex of DNA polymerase lambda with a templating 8-oxo-dG and an incoming dATP==
==Crystal structure of the pre-catalytic ternary complex of DNA polymerase lambda with a templating 8-oxo-dG and an incoming dATP==
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<StructureSection load='5iii' size='340' side='right' caption='[[5iii]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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<StructureSection load='5iii' size='340' side='right'caption='[[5iii]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5iii]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5III OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5III FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5iii]] 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=5III OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5III FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=DOC:2,3-DIDEOXYCYTIDINE-5-MONOPHOSPHATE'>DOC</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5iij|5iij]], [[5iik|5iik]], [[5iil|5iil]], [[5iim|5iim]], [[5iin|5iin]], [[5iio|5iio]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5iii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iii OCA], [https://pdbe.org/5iii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iii RCSB], [https://www.ebi.ac.uk/pdbsum/5iii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iii ProSAT]</span></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POLL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=5iii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iii OCA], [http://pdbe.org/5iii PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iii RCSB], [http://www.ebi.ac.uk/pdbsum/5iii PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iii ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/DPOLL_HUMAN DPOLL_HUMAN]] Repair polymerase. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Has both DNA polymerase and terminal transferase activities. Has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.<ref>PMID:11457865</ref> <ref>PMID:15537631</ref>
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[https://www.uniprot.org/uniprot/DPOLL_HUMAN DPOLL_HUMAN] Repair polymerase. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Has both DNA polymerase and terminal transferase activities. Has a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.<ref>PMID:11457865</ref> <ref>PMID:15537631</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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8-oxo-7,8-dihydroxy-2'-deoxyguanosine (8-oxo-dG) has high mutagenic potential as it is prone to mispair with deoxyadenine (dA). In order to maintain genomic integrity, post-replicative 8-oxo-dG:dA mispairs are removed through DNA polymerase lambda (Pol lambda)-dependent MUTYH-initiated base excision repair (BER). Here, we describe seven novel crystal structures and kinetic data that fully characterize 8-oxo-dG bypass by Pol lambda. We demonstrate that Pol lambda has a flexible active site that can tolerate 8-oxo-dG in either the anti- or syn-conformation. Importantly, we show that discrimination against the pro-mutagenic syn-conformation occurs at the extension step and identify the residue responsible for this selectivity. This residue acts as a kinetic switch, shunting repair toward long-patch BER upon correct dCMP incorporation, thus enhancing repair efficiency. Moreover, this switch also provides a potential mechanism to increase repair fidelity of MUTYH-initiated BER.
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A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG.,Burak MJ, Guja KE, Hambardjieva E, Derkunt B, Garcia-Diaz M EMBO J. 2016 Aug 1. pii: e201694332. PMID:27481934<ref>PMID:27481934</ref>
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==See Also==
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*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5iii" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Burak, M J]]
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[[Category: Large Structures]]
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[[Category: Garcia-Diaz, M]]
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[[Category: Synthetic construct]]
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[[Category: Guja, K E]]
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[[Category: Burak MJ]]
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[[Category: Transferase-dna complex]]
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[[Category: Garcia-Diaz M]]
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[[Category: Guja KE]]

Current revision

Crystal structure of the pre-catalytic ternary complex of DNA polymerase lambda with a templating 8-oxo-dG and an incoming dATP

PDB ID 5iii

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