8g9f - Revision history

OCA at 19:49, 29 May 2024

OCA — Wed, 29 May 2024 19:49:14 GMT

←Older revision		Revision as of 19:49, 29 May 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/DPOLA_XENLA DPOLA_XENLA] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes (By similarity).		[https://www.uniprot.org/uniprot/DPOLA_XENLA DPOLA_XENLA] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The mechanism by which polymerase alpha-primase (polalpha-primase) synthesizes chimeric RNA-DNA primers of defined length and composition, necessary for replication fidelity and genome stability, is unknown. Here, we report cryo-EM structures of Xenopus laevis polalpha-primase in complex with primed templates representing various stages of DNA synthesis. Our data show how interaction of the primase regulatory subunit with the primer 5' end facilitates handoff of the primer to polalpha and increases polalpha processivity, thereby regulating both RNA and DNA composition. The structures detail how flexibility within the heterotetramer enables synthesis across two active sites and provide evidence that termination of DNA synthesis is facilitated by reduction of polalpha and primase affinities for the varied conformations along the chimeric primer-template duplex. Together, these findings elucidate a critical catalytic step in replication initiation and provide a comprehensive model for primer synthesis by polalpha-primase.
		+
		+	A mechanistic model of primer synthesis from catalytic structures of DNA polymerase alpha-primase.,Mullins EA, Salay LE, Durie CL, Bradley NP, Jackman JE, Ohi MD, Chazin WJ, Eichman BF Nat Struct Mol Biol. 2024 May;31(5):777-790. doi: 10.1038/s41594-024-01227-4. , Epub 2024 Mar 15. PMID:38491139<ref>PMID:38491139</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 8g9f" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]		*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 09:31, 20 March 2024

OCA — Wed, 20 Mar 2024 09:31:58 GMT

←Older revision		Revision as of 09:31, 20 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/DPOLA_XENLA DPOLA_XENLA] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes (By similarity).		[https://www.uniprot.org/uniprot/DPOLA_XENLA DPOLA_XENLA] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes (By similarity).
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The mechanism by which polymerase alpha - primase (polalpha-primase) synthesizes chimeric RNA-DNA primers of defined length and composition, necessary for replication fidelity and genome stability, is unknown. Here, we report cryo-EM structures of polalpha-primase in complex with primed templates representing various stages of DNA synthesis. Our data show how interaction of the primase regulatory subunit with the primer 5'-end facilitates handoff of the primer to polalpha and increases polalpha processivity, thereby regulating both RNA and DNA composition. The structures detail how flexibility within the heterotetramer enables synthesis across two active sites and provide evidence that termination of DNA synthesis is facilitated by reduction of polalpha and primase affinities for the varied conformations along the chimeric primer/template duplex. Together, these findings elucidate a critical catalytic step in replication initiation and provide a comprehensive model for primer synthesis by polalpha-primase.

-	A mechanistic model of primer synthesis from catalytic structures of DNA polymerase alpha-primase.,Mullins EA, Salay LE, Durie CL, Jackman JE, Ohi MD, Chazin WJ, Eichman BF bioRxiv. 2023 Mar 16:2023.03.16.533013. doi: 10.1101/2023.03.16.533013. Preprint. PMID:36993335<ref>PMID:36993335</ref>	+	==See Also==
-		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 8g9f" style~~=~~"background-color:#fffaf0;"></div>~~	+
-	~~== References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:29, 11 October 2023

OCA — Wed, 11 Oct 2023 08:29:03 GMT

←Older revision		Revision as of 08:29, 11 October 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8g9f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G9F FirstGlance]. <br>		<table><tr><td colspan='2'>[[8g9f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G9F FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.2Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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=8g9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g9f OCA], [https://pdbe.org/8g9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g9f RCSB], [https://www.ebi.ac.uk/pdbsum/8g9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g9f ProSAT]</span></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=8g9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g9f OCA], [https://pdbe.org/8g9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g9f RCSB], [https://www.ebi.ac.uk/pdbsum/8g9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g9f ProSAT]</span></td></tr>
	</table>		</table>

OCA at 20:33, 12 April 2023

OCA — Wed, 12 Apr 2023 20:33:55 GMT

←Older revision		Revision as of 20:33, 12 April 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8g9f is ~~ON HOLD until Paper~~ Publication	+	==Complete auto-inhibitory complex of Xenopus laevis DNA polymerase alpha-primase==
		+	<StructureSection load='8g9f' size='340' side='right'caption='[[8g9f]], [[Resolution\|resolution]] 3.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8g9f]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G9F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G9F FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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=8g9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g9f OCA], [https://pdbe.org/8g9f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g9f RCSB], [https://www.ebi.ac.uk/pdbsum/8g9f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g9f ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/DPOLA_XENLA DPOLA_XENLA] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The mechanism by which polymerase alpha - primase (polalpha-primase) synthesizes chimeric RNA-DNA primers of defined length and composition, necessary for replication fidelity and genome stability, is unknown. Here, we report cryo-EM structures of polalpha-primase in complex with primed templates representing various stages of DNA synthesis. Our data show how interaction of the primase regulatory subunit with the primer 5'-end facilitates handoff of the primer to polalpha and increases polalpha processivity, thereby regulating both RNA and DNA composition. The structures detail how flexibility within the heterotetramer enables synthesis across two active sites and provide evidence that termination of DNA synthesis is facilitated by reduction of polalpha and primase affinities for the varied conformations along the chimeric primer/template duplex. Together, these findings elucidate a critical catalytic step in replication initiation and provide a comprehensive model for primer synthesis by polalpha-primase.

-	~~Authors~~:	+	A mechanistic model of primer synthesis from catalytic structures of DNA polymerase alpha-primase.,Mullins EA, Salay LE, Durie CL, Jackman JE, Ohi MD, Chazin WJ, Eichman BF bioRxiv. 2023 Mar 16:2023.03.16.533013. doi: 10.1101/2023.03.16.533013. Preprint. PMID:36993335<ref>PMID:36993335</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8g9f" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Xenopus laevis]]
		+	[[Category: Chazin WJ]]
		+	[[Category: Eichman BF]]
		+	[[Category: Mullins EA]]

OCA at 05:45, 8 March 2023

OCA — Wed, 08 Mar 2023 05:45:25 GMT

←Older revision		Revision as of 05:45, 8 March 2023
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8g9f is ON HOLD	+	The entry 8g9f is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8g9f" [edit=sysop:move=sysop]

OCA — Thu, 02 Mar 2023 04:32:06 GMT

Protected "8g9f" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:32, 2 March 2023

OCA: New page: '''Unreleased structure''' The entry 8g9f is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 02 Mar 2023 04:32:05 GMT

New page: '''Unreleased structure''' The entry 8g9f is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8g9f is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]