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| | <StructureSection load='5iim' size='340' side='right'caption='[[5iim]], [[Resolution|resolution]] 1.94Å' scene=''> | | <StructureSection load='5iim' size='340' side='right'caption='[[5iim]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5iim]] 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=5IIM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IIM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5iim]] 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=5IIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IIM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.941Å</td></tr> |
| - | <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></td></tr> | + | <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=DUP:2-DEOXYURIDINE+5-ALPHA,BETA-IMIDO-TRIPHOSPHATE'>DUP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5iii|5iii]], [[5iij|5iij]], [[5iik|5iik]], [[5iil|5iil]], [[5iin|5iin]], [[5iio|5iio]]</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=5iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iim OCA], [https://pdbe.org/5iim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iim RCSB], [https://www.ebi.ac.uk/pdbsum/5iim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iim ProSAT]</span></td></tr> |
| - | <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>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5iim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iim OCA], [http://pdbe.org/5iim PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iim RCSB], [http://www.ebi.ac.uk/pdbsum/5iim PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iim ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Burak, M J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Garcia-Diaz, M]] | + | [[Category: Burak MJ]] |
| - | [[Category: Guja, K E]] | + | [[Category: Garcia-Diaz M]] |
| - | [[Category: Transferase-dna complex]] | + | [[Category: Guja KE]] |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Garcia-Diaz M, Bebenek K, Kunkel TA, Blanco L. Identification of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in human DNA polymerase lambda: a possible role in base excision repair. J Biol Chem. 2001 Sep 14;276(37):34659-63. Epub 2001 Jul 16. PMID:11457865 doi:10.1074/jbc.M106336200
- ↑ Maga G, Ramadan K, Locatelli GA, Shevelev I, Spadari S, Hubscher U. DNA elongation by the human DNA polymerase lambda polymerase and terminal transferase activities are differentially coordinated by proliferating cell nuclear antigen and replication protein A. J Biol Chem. 2005 Jan 21;280(3):1971-81. Epub 2004 Nov 10. PMID:15537631 doi:10.1074/jbc.M411650200
- ↑ Burak MJ, Guja KE, Hambardjieva E, Derkunt B, Garcia-Diaz M. A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG. EMBO J. 2016 Aug 1. pii: e201694332. PMID:27481934 doi:http://dx.doi.org/10.15252/embj.201694332
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