1U47

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

1U47 の概要

• エントリーDOI: 10.2210/pdb1u47/pdb
• 関連するPDBエントリー: 1U45 1U48 1U49 1U4B
• 関連するBIRD辞書のPRD_ID: PRD_900003
• 分子名称: DNA primer strand, DNA template strand with 8-oxoguanine, DNA polymerase I, ... (7 entities in total)
• 機能のキーワード: dna polymerase i; dna replication; klenow fragment; protein-dna complex; 8oxoguanine; dna lesion; translation replication, transferase-dna complex, transferase/dna
• 由来する生物種: Geobacillus stearothermophilus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 74705.69

構造登録者

Hsu, G.W.,Ober, M.,Carell, T.,Beese, L.S. (登録日: 2004-07-23, 公開日: 2004-09-14, 最終更新日: 2023-08-23)

主引用文献

Hsu, G.W.,Ober, M.,Carell, T.,Beese, L.S.
Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase.
Nature, 431:217-221, 2004

PubMed Abstract: 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.

PubMed: 15322558
DOI: 10.1038/nature02908

実験手法

X-RAY DIFFRACTION (2 Å)