6m7u
From Proteopedia
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==Human DNA polymerase eta in a non-productive ternary complex with Mg2+ and dTMPNPP oppositing cdA== | ==Human DNA polymerase eta in a non-productive ternary complex with Mg2+ and dTMPNPP oppositing cdA== | ||
| - | <StructureSection load='6m7u' size='340' side='right' caption='[[6m7u]], [[Resolution|resolution]] 3.40Å' scene=''> | + | <StructureSection load='6m7u' size='340' side='right'caption='[[6m7u]], [[Resolution|resolution]] 3.40Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6m7u]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M7U OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6m7u]] is a 3 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=6M7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M7U FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=02I:(6S,7S,8S,10R)-4-AMINO-8-HYDROXY-7,8,9,10-TETRAHYDRO-6H-7,10-EPOXYAZEPINO[1,2-E]PURIN-6-YL+DIHYDROGEN+PHOSPHATE'>02I</scene>, <scene name='pdbligand=1FZ:5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]THYMIDINE'>1FZ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></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=6m7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m7u OCA], [https://pdbe.org/6m7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m7u RCSB], [https://www.ebi.ac.uk/pdbsum/6m7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m7u ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN] Defects in POLH are the cause of xeroderma pigmentosum variant type (XPV) [MIM:[https://omim.org/entry/278750 278750]; also designated as XP-V. Xeroderma pigmentosum (XP) is an autosomal recessive disease due to deficient nucleotide excision repair. It is characterized by hypersensitivity of the skin to sunlight, followed by high incidence of skin cancer and frequent neurologic abnormalities. XPV shows normal nucleotide excision repair, but an exaggerated delay in recovery of replicative DNA synthesis. Most XPV patients do not develop clinical symptoms and skin neoplasias until a later age. Clinical manifestations are limited to photo-induced deterioration of the skin and eyes.<ref>PMID:10385124</ref> <ref>PMID:10398605</ref> <ref>PMID:11032022</ref> <ref>PMID:11121129</ref> <ref>PMID:11773631</ref> |
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/POLH_HUMAN POLH_HUMAN] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Plays an important role in the repair of UV-induced pyrimidine dimers. Depending on the context, it inserts the correct base, but causes frequent base transitions and transversions. May play a role in hypermutation at immunoglobulin genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity. Targets POLI to replication foci.<ref>PMID:10385124</ref> <ref>PMID:11743006</ref> <ref>PMID:11376341</ref> <ref>PMID:14630940</ref> <ref>PMID:14734526</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Oxidatively induced DNA lesions 8,5'-cyclopurine-2'-deoxynucleosides (cdPus) are prevalent and cytotoxic by impeding DNA replication and transcription. Both the 5'R- and 5'S-diastereomers of cdPu can be removed by nucleotide excision repair; however, the 5'S-cdPu is more resistant to repair than the 5'R counterpart. Here, we report the crystal structures of human polymerase (Pol) eta bypassing 5'S-8,5'-cyclo-2'-deoxyadenosine (cdA) in insertion and the following two extension steps. The cdA-containing DNA structures vary in response to the protein environment. Supported by the "molecular splint" of Pol eta, the structure of 5'S-cdA at 1.75-A resolution reveals that the backbone is pinched toward the minor groove and the adenine base is tilted. In the templating position, the cdA takes up the extra space usually reserved for the thymine dimer, and dTTP is efficiently incorporated by Pol eta in the presence of Mn(2+) Rigid distortions of the DNA duplex by cdA, however, prevent normal base pairing and hinder immediate primer extension by Pol eta. Our results provide structural insights into the strong replication blockage effect and the mutagenic property of the cdPu lesions in cells. | ||
| + | |||
| + | Bypassing a 8,5'-cyclo-2'-deoxyadenosine lesion by human DNA polymerase eta at atomic resolution.,Weng PJ, Gao Y, Gregory MT, Wang P, Wang Y, Yang W Proc Natl Acad Sci U S A. 2018 Oct 1. pii: 1812856115. doi:, 10.1073/pnas.1812856115. PMID:30275308<ref>PMID:30275308</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6m7u" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Gao Y]] |
| - | [[Category: | + | [[Category: Weng P]] |
| - | [[Category: | + | [[Category: Yang W]] |
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Current revision
Human DNA polymerase eta in a non-productive ternary complex with Mg2+ and dTMPNPP oppositing cdA
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Categories: Homo sapiens | Large Structures | Gao Y | Weng P | Yang W
