Replication by human DNA polymerase-ι occurs by Hoogsteen base-pairing
Replication by human DNA polymerase-ι occurs by Hoogsteen base-pairing
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DOI：
10.1038/nature02692
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发表时间：
2004-07-15
期刊：
影响因子：
64.8
通讯作者：
Aggarwal, AK
中科院分区：
文献类型：
--
作者：
Nair, DT;Johnson, RE;Aggarwal, AK
几乎所有的DNA聚合酶都表现出强烈的偏好，即掺入与模板碱基形成正确的沃森克里克碱基对的核苷酸。此外，任何给定的聚合酶形成四个可能的正确碱基对的催化效率大致相同。人类DNA聚合酶-iota（hPoliota）是DNA聚合酶Y家族的成员，是这些规则的例外。hPoli掺入与模板腺嘌呤相对的正确核苷酸的效率比掺入与模板胸腺嘧啶相对的正确核苷酸的效率高几百至几千倍，而其掺入与模板鸟嘌呤或胞嘧啶相对的正确核苷酸的效率介于这两个极端之间（1-5）。在这里，我们提出的晶体结构的hPoliota绑定到模板引物和传入的核苷酸。该结构揭示了一种聚合酶，该聚合酶“专门”用于Hoogsteen碱基配对，从而将模板碱基驱动为syn构象。Hoogsteen碱基配对为hPoliota相对于不同模板碱基的不同效率和重复性提供了基础，并且它提供了一种通过干扰复制的小沟嘌呤加合物促进复制的优雅机制。
Almost all DNA polymerases show a strong preference for incorporating the nucleotide that forms the correct Watson Crick base pair with the template base. In addition, the catalytic efficiencies with which any given polymerase forms the four possible correct base pairs are roughly the same. Human DNA polymerase-iota (hPoliota), a member of the Y family of DNA polymerases, is an exception to these rules. hPoli incorporates the correct nucleotide opposite a template adenine with a several hundred to several thousand fold greater efficiency than it incorporates the correct nucleotide opposite a template thymine, whereas its efficiency for correct nucleotide incorporation opposite a template guanine or cytosine is intermediate between these two extremes(1-5). Here we present the crystal structure of hPoliota bound to a template primer and an incoming nucleotide. The structure reveals a polymerase that is 'specialized' for Hoogsteen base-pairing, whereby the templating base is driven to the syn conformation. Hoogsteen base-pairing offers a basis for the varied efficiencies and fidelities of hPoliota opposite different template bases, and it provides an elegant mechanism for promoting replication through minor-groove purine adducts that interfere with replication.