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Structure of Human DNA Polymerase Iota and the Mechanism of DNA Synthesis

机译:人类DNA聚合酶Iota的结构及DNA合成机理

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Cellular DNA polymerases belong to several families and carry out different functions. Highly accurate replica-tive DNA polymerases play the major role in cell genome replication. A number of new specialized DNA polymerases were discovered at the turn of XX-XXI centuries and have been intensively studied during the last decade. Due to the special structure of the active site, these enzymes efficiently perform synthesis on damaged DNA but are characterized by low fidelity. Human DNA polymerase iota (Pol ι) belongs to the Y-family of specialized DNA polymerases and is one of the most error-prone enzymes involved in DNA synthesis. In contrast to other DNA polymerases, Pol ι is able to use noncanonical Hoogsteen interactions for nucleotide base pairing. This allows it to incorporate nucleotides opposite various lesions in the DNA template that impair Watson-Crick interactions. Based on the data of X-ray structural analysis of Pol ι in complexes with various DNA templates and dNTP substrates, we consider the structural peculiarities of the Pol ι active site and discuss possible mechanisms that ensure the unique behavior of the enzyme on damaged and undamaged DNA.
机译:细胞DNA聚合酶属于几个家族,并执行不同的功能。高度精确的复制性DNA聚合酶在细胞基因组复制中起主要作用。在二十一世纪至二十一世纪之交,发现了许多新的专门的DNA聚合酶,并且在过去十年中进行了深入研究。由于活性位点的特殊结构,这些酶可以有效地对受损的DNA进行合成,但其保真度较低。人DNA聚合酶iota(Pol 1)属于专门的DNA聚合酶的Y家族,并且是涉及DNA合成的最容易出错的酶之一。与其他DNA聚合酶相反,Pol 1能够使用非规范的Hoogsteen相互作用进行核苷酸碱基配对。这使得它可以在DNA模板中掺入与各种损害相对的核苷酸,从而损害Watson-Crick相互作用。基于具有各种DNA模板和dNTP底物的复合物中Pol的X射线结构分析数据,我们考虑了Pol活性位点的结构特点,并讨论了确保酶在受损和未损坏时具有独特行为的可能机制。脱氧核糖核酸。

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