Lesion bypass activity of DNA polymerase θ (POLQ) is an intrinsic property of the pol domain and depends on unique sequence inserts.
Lesion bypass activity of DNA polymerase θ (POLQ) is an intrinsic property of the pol domain and depends on unique sequence inserts.
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DOI：
10.1016/j.jmb.2010.10.041
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发表时间：
2011-01-21
影响因子：
5.6
通讯作者：
Wallace SS
中科院分区：
文献类型：
--
作者：
Hogg M;Seki M;Wood RD;Doublié S;Wallace SS
PolDNA聚合酶(PolDNA)是高等真核生物基因组中编码的一种大的、多结构域的θ聚合酶。它对于维持细胞的遗传稳定性和帮助保护细胞免受电离辐射造成的DNA损伤非常重要。POLQ含有一个N端的解旋酶样域，一个功能不确定的大的中心结构域，以及一个与DNA聚合酶A家族序列相似的C端聚合酶结构域。这种酶有几个独特的性质，包括低保真度，能够插入和延伸过去的基本部位和胸腺嘧啶二醇损伤。目前尚不清楚基本部位旁路活性是否是聚合酶结构域的固有特性，或者解旋酶活性是否也是必需的。POLQ中存在的三个“插入”序列元件在任何其他A家族DNA聚合酶中都没有发现，有人认为它们可能赋予POLQ一些独特的性质。在这项工作中，我们分析了在没有每个序列插入的情况下DNA聚合酶的活性。我们发现，POL结构域在没有解旋酶样结构域或中心结构域的情况下，能够高效地绕过基本位点。插入1增加了聚合酶的加工性，但对酶的跨损伤合成特性影响很小(如果有)。然而，去除插入物2和3会降低未受损DNA上的活性，并完全取消酶绕过碱性部位或胸腺嘧啶二醇损伤的能力。
POLQ (polθ) is a large, multi-domain DNA polymerase0020encoded in higher eukaryotic genomes. It is important for maintaining genetic stability in cells and helping protect cells from DNA damage caused by ionizing radiation. POLQ contains an N-terminal helicase-like domain, a large central domain of indeterminate function, and a C-terminal polymerase domain with sequence similarity to the A-family of DNA polymerases. The enzyme has several unique properties, including low fidelity and the ability to insert and extend past abasic sites and thymine glycol lesions. It is not known whether the abasic site bypass activity is an intrinsic property of the polymerase domain, or whether helicase activity is also required. Three “insertion” sequence elements present in POLQ are not found in any other A-family DNA polymerase and it has been proposed that they may lend some unique properties to POLQ. In this work we analyzed the activity of the DNA polymerase in the absence of each sequence insertion. We find that the pol domain is capable of highly efficient bypass of abasic sites in the absence of the helicase-like or central domains. Insertion 1 increases the processivity of the polymerase but has little, if any, bearing on the translesion synthesis properties of the enzyme. However, removal of insertions 2 and 3 reduces activity on undamaged DNA and completely abrogates the ability of the enzyme to bypass abasic sites or thymine glycol lesions.
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