1u49

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[[Image:1u49.gif|left|200px]]
[[Image:1u49.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1u49 |SIZE=350|CAPTION= <scene name='initialview01'>1u49</scene>, resolution 2.15&Aring;
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The line below this paragraph, containing "STRUCTURE_1u49", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=8OG:8-OXO-2&#39;-DEOXY-GUANOSINE-5&#39;-MONOPHOSPHATE'>8OG</scene>, <scene name='pdbligand=DA:2&#39;-DEOXYADENOSINE-5&#39;-MONOPHOSPHATE'>DA</scene>, <scene name='pdbligand=DC:2&#39;-DEOXYCYTIDINE-5&#39;-MONOPHOSPHATE'>DC</scene>, <scene name='pdbligand=DG:2&#39;-DEOXYGUANOSINE-5&#39;-MONOPHOSPHATE'>DG</scene>, <scene name='pdbligand=DT:THYMIDINE-5&#39;-MONOPHOSPHATE'>DT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <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>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1u49| PDB=1u49 | SCENE= }}
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|RELATEDENTRY=[[1u45|1U45]], [[1u47|1U47]], [[1u48|1U48]], [[1u4b|1U4B]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u49 OCA], [http://www.ebi.ac.uk/pdbsum/1u49 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1u49 RCSB]</span>
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}}
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'''Adenine-8oxoguanine mismatch at the polymerase active site'''
'''Adenine-8oxoguanine mismatch at the polymerase active site'''
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==About this Structure==
==About this Structure==
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1U49 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Geobacillus_stearothermophilus Geobacillus stearothermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U49 OCA].
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U49 OCA].
==Reference==
==Reference==
Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase., Hsu GW, Ober M, Carell T, Beese LS, Nature. 2004 Sep 9;431(7005):217-21. Epub 2004 Aug 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15322558 15322558]
Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase., Hsu GW, Ober M, Carell T, Beese LS, Nature. 2004 Sep 9;431(7005):217-21. Epub 2004 Aug 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15322558 15322558]
[[Category: DNA-directed DNA polymerase]]
[[Category: DNA-directed DNA polymerase]]
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[[Category: Geobacillus stearothermophilus]]
 
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[[Category: Protein complex]]
 
[[Category: Beese, L S.]]
[[Category: Beese, L S.]]
[[Category: Carell, T.]]
[[Category: Carell, T.]]
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[[Category: Ober, M.]]
[[Category: Ober, M.]]
[[Category: 8oxoguanine]]
[[Category: 8oxoguanine]]
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[[Category: dna lesion]]
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[[Category: Dna lesion]]
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[[Category: dna polymerase i]]
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[[Category: Dna polymerase i]]
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[[Category: dna replication]]
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[[Category: Dna replication]]
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[[Category: klenow fragment]]
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[[Category: Klenow fragment]]
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[[Category: protein-dna complex]]
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[[Category: Protein-dna complex]]
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[[Category: translation replication]]
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[[Category: Translation replication]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:44:41 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:05:13 2008''
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Revision as of 07:44, 3 May 2008

Image:1u49.gif

Template:STRUCTURE 1u49

Adenine-8oxoguanine mismatch at the polymerase active site


Overview

Aerobic respiration generates reactive oxygen species that can damage guanine residues and lead to the production of 8-oxoguanine (8oxoG), the major mutagenic oxidative lesion in the genome. Oxidative damage is implicated in ageing and cancer, and its prevalence presents a constant challenge to DNA polymerases that ensure accurate transmission of genomic information. When these polymerases encounter 8oxoG, they frequently catalyse misincorporation of adenine in preference to accurate incorporation of cytosine. This results in the propagation of G to T transversions, which are commonly observed somatic mutations associated with human cancers. Here, we present sequential snapshots of a high-fidelity DNA polymerase during both accurate and mutagenic replication of 8oxoG. Comparison of these crystal structures reveals that 8oxoG induces an inversion of the mismatch recognition mechanisms that normally proofread DNA, such that the 8oxoG.adenine mismatch mimics a cognate base pair whereas the 8oxoG.cytosine base pair behaves as a mismatch. These studies reveal a fundamental mechanism of error-prone replication and show how 8oxoG, and DNA lesions in general, can form mismatches that evade polymerase error-detection mechanisms, potentially leading to the stable incorporation of lethal mutations.

About this Structure

Full crystallographic information is available from OCA.

Reference

Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase., Hsu GW, Ober M, Carell T, Beese LS, Nature. 2004 Sep 9;431(7005):217-21. Epub 2004 Aug 22. PMID:15322558 Page seeded by OCA on Sat May 3 10:44:41 2008

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