7kr3: Difference between revisions
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==== | ==Human DNA Ligase 1(E346A/E592A) Bound to a bulged DNA substrate== | ||
<StructureSection load='7kr3' size='340' side='right'caption='[[7kr3]]' scene=''> | <StructureSection load='7kr3' size='340' side='right'caption='[[7kr3]], [[Resolution|resolution]] 2.78Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7kr3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KR3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KR3 FirstGlance]. <br> | ||
</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=7kr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kr3 OCA], [https://pdbe.org/7kr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kr3 RCSB], [https://www.ebi.ac.uk/pdbsum/7kr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kr3 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.778Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</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=7kr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kr3 OCA], [https://pdbe.org/7kr3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kr3 RCSB], [https://www.ebi.ac.uk/pdbsum/7kr3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kr3 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/DNLI1_HUMAN DNLI1_HUMAN] DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
DNA ligase 1 (LIG1, Cdc9 in yeast) finalizes eukaryotic nuclear DNA replication by sealing Okazaki fragments using DNA end-joining reactions that strongly discriminate against incorrectly paired DNA substrates. Whether intrinsic ligation fidelity contributes to the accuracy of replication of the nuclear genome is unknown. Here, we show that an engineered low-fidelity LIG1(Cdc9) variant confers a novel mutator phenotype in yeast typified by the accumulation of single base insertion mutations in homonucleotide runs. The rate at which these additions are generated increases upon concomitant inactivation of DNA mismatch repair, or by inactivation of the Fen1(Rad27) Okazaki fragment maturation (OFM) nuclease. Biochemical and structural data establish that LIG1(Cdc9) normally avoids erroneous ligation of DNA polymerase slippage products, and this protection is compromised by mutation of a LIG1(Cdc9) high-fidelity metal binding site. Collectively, our data indicate that high-fidelity DNA ligation is required to prevent insertion mutations, and that this may be particularly critical following strand displacement synthesis during the completion of OFM. | |||
High-fidelity DNA ligation enforces accurate Okazaki fragment maturation during DNA replication.,Williams JS, Tumbale PP, Arana ME, Rana JA, Williams RS, Kunkel TA Nat Commun. 2021 Jan 20;12(1):482. doi: 10.1038/s41467-020-20800-1. PMID:33473124<ref>PMID:33473124</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7kr3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[DNA ligase 3D structures|DNA ligase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Tumbale PP]] | |||
[[Category: Williams RS]] | |||
Latest revision as of 18:30, 18 October 2023
Human DNA Ligase 1(E346A/E592A) Bound to a bulged DNA substrateHuman DNA Ligase 1(E346A/E592A) Bound to a bulged DNA substrate
Structural highlights
FunctionDNLI1_HUMAN DNA ligase that seals nicks in double-stranded DNA during DNA replication, DNA recombination and DNA repair. Publication Abstract from PubMedDNA ligase 1 (LIG1, Cdc9 in yeast) finalizes eukaryotic nuclear DNA replication by sealing Okazaki fragments using DNA end-joining reactions that strongly discriminate against incorrectly paired DNA substrates. Whether intrinsic ligation fidelity contributes to the accuracy of replication of the nuclear genome is unknown. Here, we show that an engineered low-fidelity LIG1(Cdc9) variant confers a novel mutator phenotype in yeast typified by the accumulation of single base insertion mutations in homonucleotide runs. The rate at which these additions are generated increases upon concomitant inactivation of DNA mismatch repair, or by inactivation of the Fen1(Rad27) Okazaki fragment maturation (OFM) nuclease. Biochemical and structural data establish that LIG1(Cdc9) normally avoids erroneous ligation of DNA polymerase slippage products, and this protection is compromised by mutation of a LIG1(Cdc9) high-fidelity metal binding site. Collectively, our data indicate that high-fidelity DNA ligation is required to prevent insertion mutations, and that this may be particularly critical following strand displacement synthesis during the completion of OFM. High-fidelity DNA ligation enforces accurate Okazaki fragment maturation during DNA replication.,Williams JS, Tumbale PP, Arana ME, Rana JA, Williams RS, Kunkel TA Nat Commun. 2021 Jan 20;12(1):482. doi: 10.1038/s41467-020-20800-1. PMID:33473124[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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