Structural basis for processive DNA synthesis by yeast DNA polymerase ε

Structural basis for processive DNA synthesis by yeast DNA polymerase ε
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DOI:
10.1038/nsmb.2712
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发表时间:
2014-01-01
影响因子:
16.8
通讯作者:
Johansson, Erik
Johansson, Erik
中科院分区:
生物学1区
文献类型:
--
作者:
Hogg, Matthew;Osterman, Pia;Johansson, Erik

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DNA聚合酶ε(Pol ε)是一种高保真聚合酶,已被证明在真核细胞的DNA复制过程中参与前导链的合成。在此,我们展示了来自酿酒酵母的Pol ε催化核心(142 kDa)与DNA和一个进入的核苷酸形成的三元结构。该结构提供了有关正确核苷酸选择以及对校对活性可能至关重要的氨基酸位置的信息。尽管缺乏其他B家族聚合酶进行高保真复制所必需的延伸的β -发夹环,但Pol ε在B家族聚合酶中具有最高的保真度。此外,催化核心具有一个新的结构域,使Pol ε能够环绕新生的双链DNA。总之,该结构为真核生物中前导链DNA合成的高持续性和高保真度提供了解释。
DNA polymerase epsilon (Pol epsilon) is a high-fidelity polymerase that has been shown to participate in leading-strand synthesis during DNA replication in eukaryotic cells. We present here a ternary structure of the catalytic core of Pol epsilon (142 kDa) from Saccharomyces cerevisiae in complex with DNA and an incoming nucleotide. This structure provides information about the selection of the correct nucleotide and the positions of amino acids that might be critical for proofreading activity. Pol epsilon has the highest fidelity among B-family polymerases despite the absence of an extended beta-hairpin loop that is required for high-fidelity replication by other B-family polymerases. Moreover, the catalytic core has a new domain that allows Pol epsilon to encircle the nascent double-stranded DNA. Altogether, the structure provides an explanation for the high processivity and high fidelity of leading-strand DNA synthesis in eukaryotes.