Yeast DNA polymerase eta makes functional contacts with the DNA minor groove only at the incoming nucleoside triphosphate.
Yeast DNA polymerase eta makes functional contacts with the DNA minor groove only at the incoming nucleoside triphosphate.
复制标题
酵母 DNA 聚合酶 eta 仅在进入的三磷酸核苷处与 DNA 小沟发生功能性接触。
DOI：
10.1073/pnas.0837578100
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发表时间：
2003
影响因子：
11.1
通讯作者：
Prakash,Satya
中科院分区：
文献类型：
--
作者：
Washington,MTodd;Wolfle,WilliamT;Spratt,ThomasE;Prakash,Louise;Prakash,Satya
DNA 聚合酶 η (Polη) 能够有效绕过多种 DNA 损伤。相对于复制聚合酶，Polη 对扭曲的 DNA 几何结构具有更大的耐受性，并且保真度较低。 X 射线晶体结构和核苷酸类似物的研究表明，与 DNA 小沟的相互作用对于复制 DNA 聚合酶的高保真度至关重要。为了确定 Polη 是否也与 DNA 小沟进行如此重要的功能接触，在这里，我们检查了当 3-脱氮鸟嘌呤（一种缺乏与蛋白质形成小沟氢键的能力的碱基类似物）在 DNA 中的不同位置取代鸟嘌呤时，对 Polη 催化的核苷酸掺入的影响。从这些研究中，我们得出结论，Polη 仅与进入核苷酸位置处的 DNA 小沟进行单一功能接触；在这方面，Polη 不同于无法通过 DNA 损伤进行复制的高保真 DNA 聚合酶。这些结果有助于解释 Polη 绕过扭曲 DNA 损伤的熟练能力。
DNA polymerase η (Polη) functions in the proficient bypass of a variety of DNA lesions. Relative to the replicative polymerases, Polη has a greater tolerance for distorted DNA geometries and possesses a low fidelity. X-ray crystal structures and studies with nucleotide analogs have implicated interactions with the DNA minor groove as being crucial for the high fidelity of replicative DNA polymerases. To determine whether Polη also makes such functionally important contacts with the DNA minor groove, here we examine the effects on Polη-catalyzed nucleotide incorporation when 3-deazaguanine, a base analog that lacks the ability to form minor-groove hydrogen bonds with the protein, is substituted for guanine at various positions in the DNA. From these studies, we conclude that Polη makes only a single functional contact with the DNA minor groove at the position of the incoming nucleotide; in this regard, Polη differs from high-fidelity DNA polymerases that are unable to replicate through DNA lesions. These results help explain the proficient ability of Polη for bypassing distorting DNA lesions.