View source for 7jkl


==Human PrimPol misinserting dATP opposite the 8-oxoguanine lesion (3'-end base of the primer strand is 2',3'-dideoxy-terminated).==
<StructureSection load='7jkl' size='340' side='right'caption='[[7jkl]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jkl]] is a 6 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=7JKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JKL 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]] 2.384&#8491;</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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene>, <scene name='pdbligand=DTP:2-DEOXYADENOSINE+5-TRIPHOSPHATE'>DTP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7jkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jkl OCA], [https://pdbe.org/7jkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jkl RCSB], [https://www.ebi.ac.uk/pdbsum/7jkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jkl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/PRIPO_HUMAN PRIPO_HUMAN] DNA primase and DNA polymerase able to initiate de novo DNA synthesis using dNTPs. Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. Involved in translesion synthesis via its primase activity by mediating uninterrupted fork progression after programmed or damage-induced fork arrest and by reinitiating DNA synthesis after dNTP depletion. Required for mitochondrial DNA (mtDNA) synthesis, suggesting it may be involved in DNA tolerance during the replication of mitochondrial DNA. Has non-overlapping function with POLH.<ref>PMID:24126761</ref> <ref>PMID:24207056</ref> <ref>PMID:24240614</ref> <ref>PMID:24267451</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
PrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative lesion 7,8-dihydro-8-oxoguanine (oxoG) via translesion synthesis, in mostly error-free manner. We present structures of PrimPol insertion complexes with a DNA template-primer and correct dCTP or erroneous dATP opposite the lesion, as well as extension complexes with C or A as a 3'-terminal primer base. We show that during the insertion of C and extension from it, the active site is unperturbed, reflecting the readiness of PrimPol to accommodate oxoG(anti). The misinsertion of A opposite oxoG(syn) also does not alter the active site, and is likely less favorable due to lower thermodynamic stability of the oxoG(syn)*A base-pair. During the extension step, oxoG(syn) induces an opening of its base-pair with A or misalignment of the 3'-A primer terminus. Together, the structures show how PrimPol accurately synthesizes DNA opposite oxidatively damaged DNA in human cells.

Structural basis of DNA synthesis opposite 8-oxoguanine by human PrimPol primase-polymerase.,Rechkoblit O, Johnson RE, Gupta YK, Prakash L, Prakash S, Aggarwal AK Nat Commun. 2021 Jun 29;12(1):4020. doi: 10.1038/s41467-021-24317-z. PMID:34188055<ref>PMID:34188055</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7jkl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Aggarwal AK]]
[[Category: Rechkoblit O]]