1u47

cytosine-8-Oxoguanine base pair at the polymerase active site

spinqualitylabelsall models 1u47, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1u47 is a 3 chain structure with sequence from Atcc 12980. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GLC, MG, SO4, FRU NonStd Res: 8OG Related: 1u45, 1u48, 1u49, 1u4b Activity: DNA-directed DNA polymerase, with EC number 2.7.7.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [DPO1_GEOSE] In addition to polymerase activity, this DNA polymerase exhibits 5' to 3' exonuclease activity. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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