Enzymatic switching for efficient and accurate translesion DNA replication
Enzymatic switching for efficient and accurate translesion DNA replication
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DOI：
10.1093/nar/gkh777
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Kunkel, TA
中科院分区：
文献类型：
--
作者：
McCulloch, SD;Kokoska, RJ;Kunkel, TA
当环丁烷嘧啶二聚体阻止DNA聚合酶（Pol） delta或epsilon的DNA复制时，一个开关发生，允许DNA聚合酶eta的翻译合成，随后另一个开关允许正常复制恢复。在本研究中，我们使用酿酒酵母Pol delta、Pol epsilon和Pol eta以及一系列匹配和不匹配的引物模板来研究这些开关，这些引物模板模拟了完全绕过顺式syn胸腺嘧啶（TT）二聚体所需的每一次结合。我们报告了一种互补的底物使用模式，表明涉及Pol eta的局部翻译合成和主要复制聚合酶的错配切除和聚合的酶开关可以解释有效和准确的二聚体旁路，已知可以抑制阳光诱导的突变和皮肤癌。
When cyclobutane pyrimidine dimers stall DNA replication by DNA polymerase (Pol) delta or epsilon, a switch occurs to allow translesion synthesis by DNA polymerase eta, followed by another switch that allows normal replication to resume. In the present study, we investigate these switches using Saccharomyces cerevisiae Pol delta, Pol epsilon and Pol eta and a series of matched and mismatched primer templates that mimic each incorporation needed to completely bypass a cis-syn thymine-thymine (TT) dimer. We report a complementary pattern of substrate use indicating that enzymatic switching involving localized translesion synthesis by Pol eta and mismatch excision and polymerization by a major replicative polymerase can account for the efficient and accurate dimer bypass known to suppress sunlight-induced mutagenesis and skin cancer.