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[[Image:2r8k.gif|left|200px]]
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{{STRUCTURE_2r8k|  PDB=2r8k  |  SCENE=  }}
'''Structure of the Eukaryotic DNA Polymerase eta in complex with 1,2-d(GpG)-cisplatin containing DNA'''


==Structure of the Eukaryotic DNA Polymerase eta in complex with 1,2-d(GpG)-cisplatin containing DNA==
<StructureSection load='2r8k' size='340' side='right'caption='[[2r8k]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2r8k]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R8K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R8K FirstGlance]. <br>
</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CPT:CISPLATIN'>CPT</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</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=2r8k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r8k OCA], [https://pdbe.org/2r8k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r8k RCSB], [https://www.ebi.ac.uk/pdbsum/2r8k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r8k ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLH_YEAST POLH_YEAST] 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. Efficiently incorporates nucleotides opposite to other UV or oxidative DNA damages like O(6)-methylguanine, 7,8-dihydro-8-oxoguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG), or p-benzoquinone DNA adducts.<ref>PMID:9409821</ref> <ref>PMID:10347143</ref> <ref>PMID:10601233</ref> <ref>PMID:9974380</ref> <ref>PMID:10924462</ref> <ref>PMID:10713149</ref> <ref>PMID:11027270</ref> <ref>PMID:10932195</ref> <ref>PMID:10725365</ref> <ref>PMID:11062246</ref> <ref>PMID:11545742</ref> <ref>PMID:11113193</ref> <ref>PMID:11238937</ref> <ref>PMID:11054429</ref> <ref>PMID:12110599</ref> <ref>PMID:11861920</ref> <ref>PMID:12899630</ref> <ref>PMID:12665597</ref> <ref>PMID:12888515</ref> <ref>PMID:12692307</ref> <ref>PMID:14527996</ref> <ref>PMID:15157108</ref> <ref>PMID:15544332</ref> <ref>PMID:15284331</ref> <ref>PMID:15333698</ref> <ref>PMID:15024063</ref> <ref>PMID:15779911</ref> <ref>PMID:16181813</ref> <ref>PMID:15520252</ref> <ref>PMID:16366567</ref> <ref>PMID:15743815</ref> <ref>PMID:16866379</ref> <ref>PMID:16387871</ref> <ref>PMID:16415180</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r8/2r8k_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2r8k ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA polymerase eta (Pol eta) is a eukaryotic lesion bypass polymerase that helps organisms to survive exposure to ultraviolet (UV) radiation, and tumor cells to gain resistance against cisplatin-based chemotherapy. It allows cells to replicate across cross-link lesions such as 1,2-d(GpG) cisplatin adducts (Pt-GG) and UV-induced cis-syn thymine dimers. We present structural and biochemical analysis of how Pol eta copies Pt-GG-containing DNA. The damaged DNA is bound in an open DNA binding rim. Nucleotidyl transfer requires the DNA to rotate into an active conformation, driven by hydrogen bonding of the templating base to the dNTP. For the 3'dG of the Pt-GG, this step is accomplished by a Watson-Crick base pair to dCTP and is biochemically efficient and accurate. In contrast, bypass of the 5'dG of the Pt-GG is less efficient and promiscuous for dCTP and dATP as a result of the presence of the rigid Pt cross-link. Our analysis reveals the set of structural features that enable Pol eta to replicate across strongly distorting DNA lesions.


==Overview==
Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta.,Alt A, Lammens K, Chiocchini C, Lammens A, Pieck JC, Kuch D, Hopfner KP, Carell T Science. 2007 Nov 9;318(5852):967-70. PMID:17991862<ref>PMID:17991862</ref>
DNA polymerase eta (Pol eta) is a eukaryotic lesion bypass polymerase that helps organisms to survive exposure to ultraviolet (UV) radiation, and tumor cells to gain resistance against cisplatin-based chemotherapy. It allows cells to replicate across cross-link lesions such as 1,2-d(GpG) cisplatin adducts (Pt-GG) and UV-induced cis-syn thymine dimers. We present structural and biochemical analysis of how Pol eta copies Pt-GG-containing DNA. The damaged DNA is bound in an open DNA binding rim. Nucleotidyl transfer requires the DNA to rotate into an active conformation, driven by hydrogen bonding of the templating base to the dNTP. For the 3'dG of the Pt-GG, this step is accomplished by a Watson-Crick base pair to dCTP and is biochemically efficient and accurate. In contrast, bypass of the 5'dG of the Pt-GG is less efficient and promiscuous for dCTP and dATP as a result of the presence of the rigid Pt cross-link. Our analysis reveals the set of structural features that enable Pol eta to replicate across strongly distorting DNA lesions.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2R8K is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R8K OCA].
</div>
<div class="pdbe-citations 2r8k" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Bypass of DNA lesions generated during anticancer treatment with cisplatin by DNA polymerase eta., Alt A, Lammens K, Chiocchini C, Lammens A, Pieck JC, Kuch D, Hopfner KP, Carell T, Science. 2007 Nov 9;318(5852):967-70. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17991862 17991862]
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
[[Category: DNA-directed DNA polymerase]]
== References ==
[[Category: Protein complex]]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Alt, A.]]
[[Category: Alt A]]
[[Category: Carell, T.]]
[[Category: Carell T]]
[[Category: Lammens, K.]]
[[Category: Lammens K]]
[[Category: Protein-cisplatin-dna-dntp complex]]
[[Category: Replication]]
[[Category: Transferase/dna complex]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 16:25:35 2008''
Retrieved from "https://proteopedia.org/2r8k"