4fjo: Difference between revisions
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==Structure of the Rev1 CTD-Rev3/7-Pol kappa RIR complex== | ==Structure of the Rev1 CTD-Rev3/7-Pol kappa RIR complex== | ||
<StructureSection load='4fjo' size='340' side='right' caption='[[4fjo]], [[Resolution|resolution]] 2.72Å' scene=''> | <StructureSection load='4fjo' size='340' side='right'caption='[[4fjo]], [[Resolution|resolution]] 2.72Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4fjo]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4fjo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FJO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FJO FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4fjo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fjo OCA], [https://pdbe.org/4fjo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fjo RCSB], [https://www.ebi.ac.uk/pdbsum/4fjo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fjo ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/REV1_MOUSE REV1_MOUSE] Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.<ref>PMID:11711549</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Lee | [[Category: Lee C-J]] | ||
[[Category: Wojtaszek | [[Category: Wojtaszek J]] | ||
[[Category: Zhou | [[Category: Zhou P]] | ||
Revision as of 22:52, 19 October 2022
Structure of the Rev1 CTD-Rev3/7-Pol kappa RIR complexStructure of the Rev1 CTD-Rev3/7-Pol kappa RIR complex
Structural highlights
FunctionREV1_MOUSE Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.[1] Publication Abstract from PubMedDNA synthesis across lesions during genomic replication requires concerted actions of specialized DNA polymerases in a potentially mutagenic process known as translesion synthesis. Current models suggest that translesion synthesis in mammalian cells is achieved in two sequential steps, with a Y-family DNA polymerase (kappa, eta, iota, or Rev1) inserting a nucleotide opposite the lesion and with the heterodimeric B-family polymerase zeta, consisting of the catalytic Rev3 subunit and the accessory Rev7 subunit, replacing the insertion polymerase to carry out primer extension past the lesion. Effective translesion synthesis in vertebrates requires the scaffolding function of the C-terminal domain (CTD) of Rev1 that interacts with the Rev1-interacting region of polymerases kappa, eta, and iota and with the Rev7 subunit of polymerase zeta. We report the purification and structure determination of a quaternary translesion polymerase complex consisting of the Rev1 CTD, the heterodimeric Pol zeta complex, and the Pol kappa Rev1-interacting region. Yeast two-hybrid assays were employed to identify important interface residues of the translesion polymerase complex. The structural elucidation of such a quaternary translesion polymerase complex encompassing both insertion and extension polymerases bridged by the Rev1 CTD provides the first molecular explanation of the essential scaffolding function of Rev1 and highlights the Rev1 CTD as a promising target for developing novel cancer therapeutics to suppress translesion synthesis. Our studies support the notion that vertebrate insertion and extension polymerases could structurally cooperate within a megatranslesion polymerase complex (translesionsome) nucleated by Rev1 to achieve efficient lesion bypass without incurring an additional switching mechanism. Structural basis of Rev1-mediated assembly of a quaternary vertebrate translesion polymerase complex consisting of Rev1, heterodimeric polymerase (Pol) zeta, and Pol kappa.,Wojtaszek J, Lee CJ, D'Souza S, Minesinger B, Kim H, D'Andrea AD, Walker GC, Zhou P J Biol Chem. 2012 Sep 28;287(40):33836-46. Epub 2012 Aug 2. PMID:22859295[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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