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| | ==DNA polymerase kappa extending beyond a bulky major benzo[a]pyrene adduct== | | ==DNA polymerase kappa extending beyond a bulky major benzo[a]pyrene adduct== |
| - | <StructureSection load='5t14' size='340' side='right' caption='[[5t14]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='5t14' size='340' side='right'caption='[[5t14]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5t14]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T14 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5T14 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5t14]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T14 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DZ4:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]ADENOSINE'>DZ4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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]] 3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=VKJ:2-DEOXY-N-[(7R,8S,9R,10S)-7,8,9-TRIHYDROXY-7,8,9,10-TETRAHYDROBENZO[PQR]TETRAPHEN-10-YL]GUANOSINE+5-(DIHYDROGEN+PHOSPHATE)'>VKJ</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DZ4:2-DEOXY-5-O-[(R)-HYDROXY{[(R)-HYDROXY(PHOSPHONOOXY)PHOSPHORYL]AMINO}PHOSPHORYL]ADENOSINE'>DZ4</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=VKJ:2-DEOXY-N-[(7R,8S,9R,10S)-7,8,9-TRIHYDROXY-7,8,9,10-TETRAHYDROBENZO[PQR]TETRAPHEN-10-YL]GUANOSINE+5-(DIHYDROGEN+PHOSPHATE)'>VKJ</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u7c|4u7c]], [[4u6p|4u6p]]</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=5t14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t14 OCA], [https://pdbe.org/5t14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t14 RCSB], [https://www.ebi.ac.uk/pdbsum/5t14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t14 ProSAT]</span></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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5t14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t14 OCA], [http://pdbe.org/5t14 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5t14 RCSB], [http://www.ebi.ac.uk/pdbsum/5t14 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5t14 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/POLK_HUMAN POLK_HUMAN]] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity.<ref>PMID:10620008</ref> <ref>PMID:11024016</ref> <ref>PMID:12145297</ref> <ref>PMID:12444249</ref> <ref>PMID:12952891</ref> <ref>PMID:14630940</ref> <ref>PMID:15533436</ref> | + | [https://www.uniprot.org/uniprot/POLK_HUMAN POLK_HUMAN] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity.<ref>PMID:10620008</ref> <ref>PMID:11024016</ref> <ref>PMID:12145297</ref> <ref>PMID:12444249</ref> <ref>PMID:12952891</ref> <ref>PMID:14630940</ref> <ref>PMID:15533436</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Human Y-family DNA polymerase kappa (polkappa) is specialized to bypass bulky lesions in DNA in an error-free way, thus protecting cells from carcinogenic bulky DNA adducts. Benzo[a]pyrene (BP) is one of the most ubiquitous polycyclic aromatic hydrocarbons and an environmental carcinogen. BP covalently modifies DNA and generates mutagenic, bulky adducts. The major BP adduct formed in cells is 10S (+)-trans-anti-BP-N2-dG adduct (BP-dG), which is associated with cancer. The molecular mechanism of how polkappa replicates BP-dG accurately is not clear. Here we report the structure of polkappa captured at the lesion-extension stage: the enzyme is extending the primer strand after the base pair containing the BP-dG adduct in the template strand at the -1 position. Polkappa accommodates the BP adduct in the nascent DNA's minor groove and keeps the adducted DNA helix in a B-form. Two water molecules cover the edge of the minor groove of the replicating base pair (0 position), which is secured by the BP ring in the -1 position in a 5' orientation. The 5' oriented BP adduct keeps correct Watson-Crick base pairing in the active site and promotes high fidelity replication. Our structural and biochemical data reveal a unique molecular basis for accurate DNA replication right after the bulky lesion BP-dG.
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| - | Structural basis of accurate replication beyond a bulky major benzo[a]pyrene adduct by human DNA polymerase kappa.,Jha V, Ling H DNA Repair (Amst). 2016 Nov 19. pii: S1568-7864(16)30359-7. doi:, 10.1016/j.dnarep.2016.11.001. PMID:27894903<ref>PMID:27894903</ref>
| + | ==See Also== |
| - | | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5t14" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA-directed DNA polymerase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Jha, V K]] | + | [[Category: Large Structures]] |
| - | [[Category: Ling, H]] | + | [[Category: Unidentified]] |
| - | [[Category: Dna repair dna replication benzopyrene ternary complex]] | + | [[Category: Jha VK]] |
| - | [[Category: Transferase-dna complex]] | + | [[Category: Ling H]] |
| Structural highlights
Function
POLK_HUMAN DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity.[1] [2] [3] [4] [5] [6] [7]
See Also
References
- ↑ Ogi T, Kato T Jr, Kato T, Ohmori H. Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein dinB. Genes Cells. 1999 Nov;4(11):607-18. PMID:10620008
- ↑ Gerlach VL, Feaver WJ, Fischhaber PL, Friedberg EC. Purification and characterization of pol kappa, a DNA polymerase encoded by the human DINB1 gene. J Biol Chem. 2001 Jan 5;276(1):92-8. PMID:11024016 doi:http://dx.doi.org/10.1074/jbc.M004413200
- ↑ Fischhaber PL, Gerlach VL, Feaver WJ, Hatahet Z, Wallace SS, Friedberg EC. Human DNA polymerase kappa bypasses and extends beyond thymine glycols during translesion synthesis in vitro, preferentially incorporating correct nucleotides. J Biol Chem. 2002 Oct 4;277(40):37604-11. Epub 2002 Jul 26. PMID:12145297 doi:10.1074/jbc.M206027200
- ↑ Haracska L, Prakash L, Prakash S. Role of human DNA polymerase kappa as an extender in translesion synthesis. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16000-5. Epub 2002 Nov 20. PMID:12444249 doi:10.1073/pnas.252524999
- ↑ Wolfle WT, Washington MT, Prakash L, Prakash S. Human DNA polymerase kappa uses template-primer misalignment as a novel means for extending mispaired termini and for generating single-base deletions. Genes Dev. 2003 Sep 1;17(17):2191-9. PMID:12952891 doi:http://dx.doi.org/10.1101/gad.1108603
- ↑ Haracska L, Prakash L, Prakash S. A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair. Genes Dev. 2003 Nov 15;17(22):2777-85. PMID:14630940 doi:10.1101/gad.1146103
- ↑ Yasui M, Suzuki N, Miller H, Matsuda T, Matsui S, Shibutani S. Translesion synthesis past 2'-deoxyxanthosine, a nitric oxide-derived DNA adduct, by mammalian DNA polymerases. J Mol Biol. 2004 Nov 26;344(3):665-74. PMID:15533436 doi:S0022-2836(04)01222-7
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