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7kt9

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DNA Polymerase Mu, 8-oxodGTP:At Product State Ternary Complex, 50 mM Mg2+ (960min)

Structural highlights

7kt9 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.482Å
Ligands:	, , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPOLM_HUMAN Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Oxidized dGTP (8-oxo-7,8-dihydro-2 -deoxyguanosine triphosphate, 8-oxodGTP) insertion by DNA polymerases strongly promotes cancer and human disease. How DNA polymerases discriminate against oxidized and undamaged nucleotides, especially in error-prone double strand break (DSB) repair, is poorly understood. High-resolution time-lapse X-ray crystallography snapshots of DSB repair polymerase mu undergoing DNA synthesis reveal that a third active site metal promotes insertion of oxidized and undamaged dGTP in the canonical anti-conformation opposite template cytosine. The product metal bridged O8 with product oxygens, and was not observed in the syn-conformation opposite template adenine (At). Rotation of At into the syn-conformation enabled undamaged dGTP misinsertion. Exploiting metal and substrate dynamics in a rigid active site allows 8-oxodGTP to circumvent polymerase fidelity safeguards to promote pro-mutagenic double strand break repair.

Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.,Jamsen JA, Sassa A, Shock DD, Beard WA, Wilson SH Nat Commun. 2021 Apr 6;12(1):2059. doi: 10.1038/s41467-021-21354-6. PMID:33824325^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nick McElhinny SA, Ramsden DA. Polymerase mu is a DNA-directed DNA/RNA polymerase. Mol Cell Biol. 2003 Apr;23(7):2309-15. PMID:12640116
↑ Ruiz JF, Juarez R, Garcia-Diaz M, Terrados G, Picher AJ, Gonzalez-Barrera S, Fernandez de Henestrosa AR, Blanco L. Lack of sugar discrimination by human Pol mu requires a single glycine residue. Nucleic Acids Res. 2003 Aug 1;31(15):4441-9. PMID:12888504
↑ Capp JP, Boudsocq F, Besnard AG, Lopez BS, Cazaux C, Hoffmann JS, Canitrot Y. Involvement of DNA polymerase mu in the repair of a specific subset of DNA double-strand breaks in mammalian cells. Nucleic Acids Res. 2007;35(11):3551-60. Epub 2007 May 5. PMID:17483519 doi:http://dx.doi.org/10.1093/nar/gkm243
↑ DeRose EF, Clarkson MW, Gilmore SA, Galban CJ, Tripathy A, Havener JM, Mueller GA, Ramsden DA, London RE, Lee AL. Solution structure of polymerase mu's BRCT Domain reveals an element essential for its role in nonhomologous end joining. Biochemistry. 2007 Oct 30;46(43):12100-10. Epub 2007 Oct 4. PMID:17915942 doi:10.1021/bi7007728
↑ Jamsen JA, Sassa A, Shock DD, Beard WA, Wilson SH. Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide. Nat Commun. 2021 Apr 6;12(1):2059. doi: 10.1038/s41467-021-21354-6. PMID:33824325 doi:http://dx.doi.org/10.1038/s41467-021-21354-6

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7kt9"

Categories: Homo sapiens | Large Structures | Jamsen JA | Wilson SH

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[7kt9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KT9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KT9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOA:GLYCOLIC+ACID'>GOA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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]] 1.482&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OG:8-OXO-2-DEOXY-GUANOSINE-5-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOA:GLYCOLIC+ACID'>GOA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=7kt9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kt9 OCA], [https://pdbe.org/7kt9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kt9 RCSB], [https://www.ebi.ac.uk/pdbsum/7kt9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kt9 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/DPOLM_HUMAN DPOLM_HUMAN]] Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.<ref>PMID:12640116</ref> <ref>PMID:12888504</ref> <ref>PMID:17483519</ref> <ref>PMID:17915942</ref>
+[https://www.uniprot.org/uniprot/DPOLM_HUMAN DPOLM_HUMAN] Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.<ref>PMID:12640116</ref> <ref>PMID:12888504</ref> <ref>PMID:17483519</ref> <ref>PMID:17915942</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7kt9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
 == References ==
 <references/>

7kt9

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Current revision

DNA Polymerase Mu, 8-oxodGTP:At Product State Ternary Complex, 50 mM Mg2+ (960min)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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