Implications of N7-hydrogen and C8-keto on the base pairing, mutagenic potential and repair of 8-oxo-2′-deoxy-adenosine: Investigation by nucleotide analogues
Implications of N7-hydrogen and C8-keto on the base pairing, mutagenic potential and repair of 8-oxo-2′-deoxy-adenosine: Investigation by nucleotide analogues
复制标题
N7-氢和C8-酮对8-氧代-2-脱氧-腺苷的碱基配对、诱变潜力和修复的影响：通过核苷酸类似物进行研究
DOI：
10.1016/j.bioorg.2022.106029
复制
发表时间：
2022
影响因子：
5.1
通讯作者：
Yizhen Yin
中科院分区：
文献类型：
--
作者：
Junjie Wu;Mengmeng Zhang;Lulu Song;Yahong Tan;Yosuke Taniguchi;Christopher John Hipolito;Youming Zhang;Yizhen Yin
氧化损伤，如8-氧代-dG和8-氧代-dA，是从暴露于活性氧连续产生。虽然8-oxo-dG已被广泛研究，但8-oxo-dA直到最近才受到如此多的关注。在此，我们报道了在7位和8位具有不同取代的dA、8-oxo-dA、7-deaza-dA、8-Br-dA和8-Br-7-deaza-dA的双链DNA的合成，以研究N7-氢和C8-酮对碱基配对偏好的影响，碱基配对研究表明，8-oxo-dA的极性N7-氢和C8-酮，而不是顺式偏好，可能是8-oxo-dA与dG形成稳定碱基对所必需的。使用KF-exo−和人类DNA聚合酶β的插入和延伸研究表明，与8-oxo-dA相对的有效dGTP插入和超过8-oxo-dA：dG的延伸不仅取决于与dG的稳定碱基对，还取决于聚合酶活性位点的灵活性。8-oxo-dA中的N7位氢或7-deaza-dA和8-Br-7-deaza-dA中的C7位氢对hOGG 1的识别具有重要作用，尽管7-deaza-dA和8-Br-7-deaza-dA的切除效率远低于8-oxo-dA。
Oxidative lesions, such as 8-oxo-dG and 8-oxo-dA, are continuously generated from exposure to reactive oxygen species. While 8-oxo-dG has been extensively studied, 8-oxo-dA has not received as much attention until recently. Herein, we report the synthesis of duplex DNAs incorporating dA, 8-oxo-dA, 7-deaza-dA, 8-Br-dA, and 8-Br-7-deaza-dA, which have different substitutions at 7- and 8-position, for the investigation into the implications of N7-hydrogen and C8-keto on the base pairing preference, mutagenic potential and repair of 8-oxo-dA. Base pairing study suggested that the polar N7-hydrogen and C8-keto of 8-oxo-dA, rather than thesyn-preference, might be essential for 8-oxo-dA to form a stable base pair with dG. Insertion and extension studies using KF-exo−and human DNA polymerase β indicated that the efficient dGTP insertion opposite 8-oxo-dA and extension past 8-oxo-dA:dG are contingent upon not only the stable base pair with dG, but also the flexibility of the active site in polymerase. The N7-hydrogen in 8-oxo-dA or C7-hydrogen in 7-deaza-dA and 8-Br-7-deaza-dA was suggested to be important for the recognition by hOGG1, although the excision efficiencies of 7-deaza-dA and 8-Br-7-deaza-dA were much lower than 8-oxo-dA. This study provides an insight into the structure-function relationship of 8-oxo-dA by nucleotide analogues.