View source for 8uks


==RNA polymerase II elongation complex with Fapy-dG lesion soaking with CTP before chemistry==
<StructureSection load='8uks' size='340' side='right'caption='[[8uks]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8uks]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C] 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=8UKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UKS 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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTP:CYTIDINE-5-TRIPHOSPHATE'>CTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=WVQ:N-[(5E)-2-amino-5-(formylimino)-6-oxo-5,6-dihydropyrimidin-4-yl]-2-deoxy-5-O-phosphono-beta-D-erythro-pentofuranosylamine'>WVQ</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8uks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uks OCA], [https://pdbe.org/8uks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uks RCSB], [https://www.ebi.ac.uk/pdbsum/8uks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uks ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Oxidative DNA lesions cause significant detrimental effects on a living species. Two major DNA lesions resulting from dG oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OxodGuo) and formamidopyrimidine (Fapy.dG), are produced from a common chemical intermediate. Fapy.dG is formed in comparable yields under oxygen-deficient conditions. Replicative bypass of Fapy.dG in human cells is more mutagenic than that of 8-OxodGuo. Despite the biological importance of transcriptional mutagenesis, there are no reports of the effects of Fapy.dG on RNA polymerase II (Pol II) activity. Here we perform comprehensive kinetic studies to investigate the impact of Fapy.dG on three key transcriptional fidelity checkpoint steps by Pol II: insertion, extension, and proofreading steps. The ratios of error-free versus error-prone incorporation opposite Fapy.dG are significantly reduced in comparison with undamaged dG. Similarly, Fapy.dG:A mispair is extended with comparable efficiency as that of the error-free, Fapy.dG:C base pair. The alpha- and beta-configurational isomers of Fapy.dG have distinct effects on Pol II insertion and extension. Pol II can preferentially cleave error-prone products by proofreading. To further understand the structural basis of transcription processing of Fapy.dG, five different structures were solved, including Fapy.dG template-loading state (apo), error-free cytidine triphosphate (CTP) binding state (prechemistry), error-prone ATP binding state (prechemistry), error-free Fapy.dG:C product state (postchemistry), and error-prone Fapy.dG:A product state (postchemistry), revealing distinctive nucleotide binding and product states. Taken together, our study provides a comprehensive mechanistic framework for better understanding how Fapy.dG lesions impact transcription and subsequent pathological consequences.

Molecular Mechanism of RNA Polymerase II Transcriptional Mutagenesis by the Epimerizable DNA Lesion, Fapy.dG.,Gao S, Hou P, Oh J, Wang D, Greenberg MM J Am Chem Soc. 2024 Mar 6;146(9):6274-6282. doi: 10.1021/jacs.3c14476. Epub 2024 , Feb 23. PMID:38393762<ref>PMID:38393762</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8uks" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Synthetic construct]]
[[Category: Hou P]]
[[Category: Oh J]]
[[Category: Wang D]]