The high fidelity and unique error signature of human DNA polymerase epsilon.
The high fidelity and unique error signature of human DNA polymerase epsilon.
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DOI：
10.1093/nar/gkq1034
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发表时间：
2011-03
影响因子：
14.9
通讯作者：
Pursell ZF
中科院分区：
文献类型：
--
作者：
Korona DA;Lecompte KG;Pursell ZF
真核生物中大量复制的DNA合成是非常准确和高效的，这主要是因为有两种DNA聚合酶：Polsδ和ε。这些酶的高保真度是由于它们固有的碱基选择性和校对核酸外切酶活性，当再加上复制后错配修复时，有助于将人类突变率保持在每个基因组复制不到一个突变。降低聚合酶保真度的条件会导致突变增加，并可能导致老鼠患上癌症。虽然酵母POLε已经被很好地描述，但人类POLε仍然知之甚少。在这里，我们提出了第一份关于人类POLε保真度的报告。我们发现，人的POLε即使在没有3‘→5’外切核校对的情况下也能高保真地进行DNA合成，而且比酵母POLε的准确性要高得多。尽管它的误差范围与酵母POLε相似，但也有几个值得注意的例外。这包括人类对T→A的酶的偏好，而不是A→T的易位。与其他复制型DNA聚合酶相比，人的POLε在复制4-5个碱基的同源核苷酸序列时尤其准确。人POLε的碱基对替换特异性和移码错误的高保真度与人POLδ的错误截然不同。
Bulk replicative DNA synthesis in eukaryotes is highly accurate and efficient, primarily because of two DNA polymerases (Pols): Pols δ and ε. The high fidelity of these enzymes is due to their intrinsic base selectivity and proofreading exonuclease activity which, when coupled with post-replication mismatch repair, helps to maintain human mutation rates at less than one mutation per genome duplication. Conditions that reduce polymerase fidelity result in increased mutagenesis and can lead to cancer in mice. Whereas yeast Pol ε has been well characterized, human Pol ε remains poorly understood. Here, we present the first report on the fidelity of human Pol ε. We find that human Pol ε carries out DNA synthesis with high fidelity, even in the absence of its 3′→5′ exonucleolytic proofreading and is significantly more accurate than yeast Pol ε. Though its spectrum of errors is similar to that of yeast Pol ε, there are several notable exceptions. These include a preference of the human enzyme for T→A over A→T transversions. As compared with other replicative DNA polymerases, human Pol ε is particularly accurate when copying homonucleotide runs of 4–5 bases. The base pair substitution specificity and high fidelity for frameshift errors observed for human Pol ε are distinct from the errors made by human Pol δ.
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影响因子：
4.8
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