6s1c: Difference between revisions
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==P3221 crystal form of the Ctf18-1-8/Pol2(1-528) complex== | ==P3221 crystal form of the Ctf18-1-8/Pol2(1-528) complex== | ||
<StructureSection load='6s1c' size='340' side='right'caption='[[6s1c]]' scene=''> | <StructureSection load='6s1c' size='340' side='right'caption='[[6s1c]], [[Resolution|resolution]] 6.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S1C OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6S1C FirstGlance]. <br> | <table><tr><td colspan='2'>[[6s1c]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6S1C OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6S1C FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6s1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s1c OCA], [http://pdbe.org/6s1c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s1c RCSB], [http://www.ebi.ac.uk/pdbsum/6s1c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s1c ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POL2, DUN2, YNL262W, N0825 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), DCC1, YCL016C, YCL16C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), CTF8, YHR191C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), CTF18, CHL12, YMR078C, YM9582.03C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_DNA_polymerase DNA-directed DNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.7 2.7.7.7] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6s1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6s1c OCA], [http://pdbe.org/6s1c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6s1c RCSB], [http://www.ebi.ac.uk/pdbsum/6s1c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6s1c ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/CTF18_YEAST CTF18_YEAST]] Essential for the fidelity of chromosome transmission. Required for the DNA replication block checkpoint. Component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA.<ref>PMID:11287619</ref> <ref>PMID:11389843</ref> <ref>PMID:11486023</ref> <ref>PMID:15964801</ref> [[http://www.uniprot.org/uniprot/DPOE_YEAST DPOE_YEAST]] DNA polymerase epsilon (DNA polymerase II) participates in chromosomal DNA replication. It is required during synthesis of the leading and lagging DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. It has 3'-5' proofreading exonuclease activity that correct errors arising during DNA replication. It is also involved in DNA synthesis during DNA repair.<ref>PMID:12124389</ref> [[http://www.uniprot.org/uniprot/CTF8_YEAST CTF8_YEAST]] Essential for the fidelity of chromosome transmission. Required for the DNA replication block checkpoint. Component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA.<ref>PMID:11389843</ref> <ref>PMID:15964801</ref> [[http://www.uniprot.org/uniprot/DCC1_YEAST DCC1_YEAST]] Component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA.<ref>PMID:11389843</ref> <ref>PMID:15964801</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The eukaryotic replisome must faithfully replicate DNA and cope with replication fork blocks and stalling, while simultaneously promoting sister chromatid cohesion. Ctf18-RFC is an alternative PCNA loader that links all these processes together by an unknown mechanism. Here, we use integrative structural biology combined with yeast genetics and biochemistry to highlight the specific functions that Ctf18-RFC plays within the leading strand machinery via an interaction with the catalytic domain of DNA Pol . We show that a large and unusually flexible interface enables this interaction to occur constitutively throughout the cell cycle and regardless of whether forks are replicating or stalled. We reveal that, by being anchored to the leading strand polymerase, Ctf18-RFC can rapidly signal fork stalling to activate the S phase checkpoint. Moreover, we demonstrate that, independently of checkpoint signaling or chromosome cohesion, Ctf18-RFC functions in parallel to Chl1 and Mrc1 to protect replication forks and cell viability. | |||
Ctf18-RFC and DNA Pol form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication.,Stokes K, Winczura A, Song B, Piccoli G, Grabarczyk DB Nucleic Acids Res. 2020 Aug 20;48(14):8128-8145. doi: 10.1093/nar/gkaa541. PMID:32585006<ref>PMID:32585006</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6s1c" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Baker's yeast]] | |||
[[Category: DNA-directed DNA polymerase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Grabarczyk | [[Category: Grabarczyk, D B]] | ||
[[Category: Dna polymerase]] | |||
[[Category: Pcna loader]] | |||
[[Category: Protein complex]] | |||
[[Category: Replication]] | |||
Revision as of 11:20, 20 January 2021
P3221 crystal form of the Ctf18-1-8/Pol2(1-528) complexP3221 crystal form of the Ctf18-1-8/Pol2(1-528) complex
Structural highlights
Function[CTF18_YEAST] Essential for the fidelity of chromosome transmission. Required for the DNA replication block checkpoint. Component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA.[1] [2] [3] [4] [DPOE_YEAST] DNA polymerase epsilon (DNA polymerase II) participates in chromosomal DNA replication. It is required during synthesis of the leading and lagging DNA strands at the replication fork and binds at/or near replication origins and moves along DNA with the replication fork. It has 3'-5' proofreading exonuclease activity that correct errors arising during DNA replication. It is also involved in DNA synthesis during DNA repair.[5] [CTF8_YEAST] Essential for the fidelity of chromosome transmission. Required for the DNA replication block checkpoint. Component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA.[6] [7] [DCC1_YEAST] Component of the RFC-like complex CTF18-RFC which is required for efficient establishment of chromosome cohesion during S-phase and may load or unload POL30/PCNA. During a clamp loading circle, the RFC:clamp complex binds to DNA and the recognition of the double-stranded/single-stranded junction stimulates ATP hydrolysis by RFC. The complex presumably provides bipartite ATP sites in which one subunit supplies a catalytic site for hydrolysis of ATP bound to the neighboring subunit. Dissociation of RFC from the clamp leaves the clamp encircling DNA.[8] [9] Publication Abstract from PubMedThe eukaryotic replisome must faithfully replicate DNA and cope with replication fork blocks and stalling, while simultaneously promoting sister chromatid cohesion. Ctf18-RFC is an alternative PCNA loader that links all these processes together by an unknown mechanism. Here, we use integrative structural biology combined with yeast genetics and biochemistry to highlight the specific functions that Ctf18-RFC plays within the leading strand machinery via an interaction with the catalytic domain of DNA Pol . We show that a large and unusually flexible interface enables this interaction to occur constitutively throughout the cell cycle and regardless of whether forks are replicating or stalled. We reveal that, by being anchored to the leading strand polymerase, Ctf18-RFC can rapidly signal fork stalling to activate the S phase checkpoint. Moreover, we demonstrate that, independently of checkpoint signaling or chromosome cohesion, Ctf18-RFC functions in parallel to Chl1 and Mrc1 to protect replication forks and cell viability. Ctf18-RFC and DNA Pol form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication.,Stokes K, Winczura A, Song B, Piccoli G, Grabarczyk DB Nucleic Acids Res. 2020 Aug 20;48(14):8128-8145. doi: 10.1093/nar/gkaa541. PMID:32585006[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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