OCA at 10:37, 2 August 2023

2023-08-02T10:37:48Z

←Older revision		Revision as of 10:37, 2 August 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8evf is ~~ON HOLD~~ until ~~Paper~~ Publication	+	==HUMAN DNA POLYMERASE ETA EXTENSION COMPLEX WITH AN INCOMING DCTP==
		+	<StructureSection load='8evf' size='340' side='right'caption='[[8evf]], [[Resolution\|resolution]] 2.87Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8evf]] is a 3 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=8EVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8EVF 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]] 2.87Å</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=DCP:2-DEOXYCYTIDINE-5-TRIPHOSPHATE'>DCP</scene>, <scene name='pdbligand=X6H:(4aM,9M)-3-(2-deoxy-5-O-phosphono-beta-D-erythro-pentofuranosyl)-3,5-dihydropyrimido[1,2-a]purine-6,10-dione'>X6H</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=8evf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8evf OCA], [https://pdbe.org/8evf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8evf RCSB], [https://www.ebi.ac.uk/pdbsum/8evf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8evf ProSAT]</span></td></tr>
		+	</table>
		+	== 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 ==
		+	[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 ==
		+	The DNA adduct 6-oxo-M(1)dG, (3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-6-oxo-pyrimido(1,2alpha)purin-10(3H)-one) is formed in the genome via oxidation of the peroxidation-derived adduct M(1)dG. However, the effect of 6-oxo-M(1)dG adducts on subsequent DNA replication is unclear. Here we investigated the ability of the human Y-family polymerase hPol eta to bypass 6-oxo-M(1)dG. Using steady-state kinetics and analysis of DNA extension products by LC-MS/MS, we found hPol eta preferentially inserts a dAMP or dGMP nucleotide into primer-templates across from the 6-oxo-M(1)dG adduct, with dGMP being slightly preferred. We also show primer-templates with a 3'-terminal dGMP or dAMP across from 6-oxo-M(1)dG were extended to a greater degree than primers with a dCMP or dTMP across from the adduct. In addition, we explored the structural basis for bypass of 6-oxo-M(1)dG by hPol eta using X-ray crystallography of both an insertion-stage and an extension-stage complex. In the insertion-stage complex, we observed that the incoming dCTP opposite 6-oxo-M(1)dG, although present during crystallization, was not present in the active site. We found the adduct does not interact with residues in the hPol eta active site, but rather forms stacking interactions with the base pair immediately 3' to the adduct. In the extension-stage complex, we observed the 3' hydroxyl group of the primer strand dGMP across from 6-oxo-M(1)dG is not positioned correctly to form a phosphodiester bond with the incoming dCTP. Taken together, these results indicate 6-oxo-M(1)dG forms a strong block to DNA replication by hPol eta and provide a structural basis for its blocking ability.

-	~~Authors: Pallan~~, ~~P.S~~., ~~Egli~~, M.	+	The peroxidation-derived DNA adduct, 6-oxo-M(1)dG, is a strong block to replication by human DNA polymerase eta.,Richie-Jannetta R, Pallan P, Kingsley PJ, Kamdar N, Egli M, Marnett LJ J Biol Chem. 2023 Jul 17:105067. doi: 10.1016/j.jbc.2023.105067. PMID:37468099<ref>PMID:37468099</ref>

-	~~Description~~: ~~HUMAN DNA POLYMERASE ETA EXTENSION COMPLEX WITH AN INCOMING DCTP~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Pallan, P.S~~]]	+	<div class="pdbe-citations 8evf" style="background-color:#fffaf0;"></div>
-	[[Category: Egli, M]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Egli M]]
		+	[[Category: Pallan PS]]

OCA at 05:00, 18 January 2023

2023-01-18T05:00:25Z

←Older revision		Revision as of 05:00, 18 January 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8evf is ON HOLD	+	The entry 8evf is ON HOLD until Paper Publication

	Authors: Pallan, P.S., Egli, M.		Authors: Pallan, P.S., Egli, M.

OCA: Protected "8evf" [edit=sysop:move=sysop]

2022-10-26T04:07:21Z

Protected "8evf" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:07, 26 October 2022

OCA: New page: '''Unreleased structure''' The entry 8evf is ON HOLD Authors: Pallan, P.S., Egli, M. Description: HUMAN DNA POLYMERASE ETA EXTENSION COMPLEX WITH AN INCOMING DCTP [[Category: Unrelease...

2022-10-26T04:07:21Z

New page: '''Unreleased structure''' The entry 8evf is ON HOLD Authors: Pallan, P.S., Egli, M. Description: HUMAN DNA POLYMERASE ETA EXTENSION COMPLEX WITH AN INCOMING DCTP [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 8evf is ON HOLD

Authors: Pallan, P.S., Egli, M.

Description: HUMAN DNA POLYMERASE ETA EXTENSION COMPLEX WITH AN INCOMING DCTP
[[Category: Unreleased Structures]]
[[Category: Pallan, P.S]]
[[Category: Egli, M]]

8evf - Revision history

OCA at 10:37, 2 August 2023

OCA at 05:00, 18 January 2023

OCA: Protected "8evf" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8evf is ON HOLD Authors: Pallan, P.S., Egli, M. Description: HUMAN DNA POLYMERASE ETA EXTENSION COMPLEX WITH AN INCOMING DCTP [[Category: Unrelease...