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首页> 外文期刊>Biochemistry >Evidence for the Kinetic Partitioning of Polymerase Activity on G-Quadruplex DNA
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Evidence for the Kinetic Partitioning of Polymerase Activity on G-Quadruplex DNA

机译：G-四链体DNA上聚合酶活性的动力学分区的证据。

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摘要

We have investigated the action of the human DNA polymerase epsilon (hpol epsilon) and eta (hpol eta) catalytic cores on G-quadruplex (G4) DNA substrates derived from the promoter of the c-MYC proto-oncogene. The translesion enzyme hpol eta exhibits a 6.2-fold preference for binding to G4 DNA over non-G4 DNA, while hpol 8 binds both G4 and non-G4 substrates with nearly equal affinity. Kinetic analysis of single-nucleotide insertion by hpol eta reveals that it is able to maintain >25% activity on G4 substrates compared to non-G4 DNA substrates, even when the primer template junction is positioned directly adjacent to G22 (the first tetrad-associated guanine in the c-MYC G4 motif). Surprisingly, hpol eta fidelity increases similar to 15-fold when copying G22. By way of comparison, hpol epsilon retains similar to 4% activity and has a 33-fold decrease in fidelity when copying G22. The fidelity of hpol eta is similar to 100-fold greater than that of hpol epsilon when comparing the misinsertion frequencies of the two enzymes opposite a tetrad-associated guanine. The kinetic differences observed for the B- and Y-family pols on G4 DNA support a model in which a simple kinetic switch between replicative and TLS pols could help govern fork progress during G4 DNA replication.
机译：我们已经研究了人类DNA聚合酶epsilon（hpol epsilon）和eta（hpol eta）催化核心对衍生自c-MYC原癌基因启动子的G-四链体（G4）DNA底物的作用。与非G4 DNA相比，跨病变酶hpol eta与G4 DNA的结合表现出6.2倍的偏好，而hpol 8与G4和非G4底物的结合亲和力几乎相等。通过hpol eta进行单核苷酸插入的动力学分析表明，与非G4 DNA底物相比，它能够在G4底物上保持> 25％的活性，即使引物模板连接位于与G22直接相邻的位置（第一个四联体） c-MYC G4基序中的鸟嘌呤）。出人意料的是，复制G22时，hpol eta保真度增加了大约15倍。作为比较，hpolε保留了接近4％的活性，复制G22时保真度降低了33倍。当比较与四联体鸟嘌呤相对的两种酶的插入错误频率时，hpol eta的保真度比hpolε的保真度高100倍。在G4 DNA上观察到的B和Y家族pol的动力学差异支持了一个模型，在该模型中，复制性和TLS pol之间的简单动力学切换可以帮助控制G4 DNA复制期间的叉子进程。

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