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首页> 外文期刊>Molecular and Cellular Biology >Efficient and Error-Free Replication Past a Minor-Groove DNA Adduct by the Sequential Action of Human DNA Polymerases ι and κ
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Efficient and Error-Free Replication Past a Minor-Groove DNA Adduct by the Sequential Action of Human DNA Polymerases ι and κ

机译：通过人类DNA聚合酶η和κ的顺序作用，经过小沟DNA加合物的高效且无错复制

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DNA polymerase ι (Polι) is a member of the Y family of DNA polymerases, which promote replication through DNA lesions. The role of Polι in lesion bypass, however, has remained unclear. Polι is highly unusual in that it incorporates nucleotides opposite different template bases with very different efficiencies and fidelities. Since interactions of DNA polymerases with the DNA minor groove provide for the nearly equivalent efficiencies and fidelities of nucleotide incorporation opposite each of the four template bases, we considered the possibility that Polι differs from other DNA polymerases in not being as sensitive to distortions of the minor groove at the site of the incipient base pair and that this enables it to incorporate nucleotides opposite highly distorting minor-groove DNA adducts. To check the validity of this idea, we examined whether Polι could incorporate nucleotides opposite the γ-HOPdG adduct, which is formed from an initial reaction of acrolein with the N2 of guanine. We show here that Polι incorporates a C opposite this adduct with nearly the same efficiency as it does opposite a nonadducted template G residue. The subsequent extension step, however, is performed by Polκ, which efficiently extends from the C incorporated opposite the adduct. Based upon these observations, we suggest that an important biological role of Polι and Polκ is to act sequentially to carry out the efficient and accurate bypass of highly distorting minor-groove DNA adducts of the purine bases.
机译：DNA聚合酶I（PolI）是DNA聚合酶的Y家族的成员，其促进通过DNA损伤的复制。然而，Poli在病变旁路中的作用仍不清楚。极不寻常之处在于，它以不同的效率和保真度掺入了与不同模板碱基相对的核苷酸。由于DNA聚合酶与DNA小沟的相互作用提供了与四个模板碱基相对的几乎相同的核苷酸掺入效率和保真度，因此我们认为Polι与其他DNA聚合酶不同的可能性是，它对次要小片段的扭曲不那么敏感在起始碱基对的位点形成一个小沟，这使它能够掺入与高度扭曲的小沟槽DNA加合物相对的核苷酸。为了检验该想法的有效性，我们检查了Pol 1是否可以掺入与γ-HOPdG加合物相对的核苷酸，该加合物是由丙烯醛与鸟嘌呤的N 2 的初始反应形成的。我们在此表明​​，Poly以与与非加合物模板G残基相反的效率几乎相同的效率结合了与该加合物相反的C。但是，随后的延伸步骤是由Polκ进行的，Polκ从与加合物相反的C中有效地延伸出来。基于这些观察，我们建议Pol 1和Polκ的重要生物学作用是依次起作用以对嘌呤碱基的高度扭曲的小沟槽DNA加合物进行有效而准确的旁路。

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