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首页> 外文期刊>Genes to cells : >Error-prone and inefficient replication across 8-hydroxyguanine (8-oxoguanine) in human and mouse ras gene fragments by DNA polymerase kappa.
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Error-prone and inefficient replication across 8-hydroxyguanine (8-oxoguanine) in human and mouse ras gene fragments by DNA polymerase kappa.

机译：DNA聚合酶kappa在人和小鼠ras基因片段中的8-羟基鸟嘌呤（8-氧代鸟嘌呤）上容易出错且复制效率低下。

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摘要

Using fragments of human c-Ha-ras and mouse Ha-ras1 genes containing 8-hydroxyguanine (8-OH-G) in hypermutagenic codon 12, we analyzed the kinetics of DNA synthesis catalyzed by human Polkappa. This translesion DNA polymerase, belonging to the Y-family, was found to be moderately inhibited by the presence of 8-OH-G on either mouse or human templates. From our previous results, inhibition of various polymerases by 8-OH-G increases in the following order: Poleta < Polkappa < Polbeta < Polalpha, showing that major replicative and repair polymerases are more sensitive to this lesion than enzymes belonging to the Y-family. In the direct mutagenesis experiments, Polkappa was found to be more mutagenic than Poleta studied previously: it inserted dAMP more efficiently than dCMP opposite 8-OH-G. Polkappa was also able to cause indirect mispair ('action-at-a-distance' mutagenesis), this effect being more distinct on mouse templates. Two adjacent 8-OH-G residues in codon 12 inhibited Polkappa moderately and induced misincorporation of dAMP. However, this effect was not comparable to the strong relaxation of the enzyme specificity, observed previously in the case of Poleta. Polkappa catalyzed incorporation (and misincorporation of dAMP) much more efficiently on mouse templates, human DNA fragments being distinctly worse substrates. Interestingly, in direct mutagenesis systems, the preference for dAMP over dCMP was nearly the same on mouse and human templates.
机译：在高诱变密码子12中使用人类c-Ha-ras和含有8-羟基鸟嘌呤（8-OH-G）的小鼠Ha-ras1基因的片段，我们分析了人类Polkappa催化的DNA合成动力学。发现属于小鼠Y家族的这种跨病变的DNA聚合酶被小鼠或人类模板上的8-OH-G适度抑制。从我们先前的结果来看，8-OH-G对各种聚合酶的抑制作用按以下顺序增加：Poleta

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