酵母DNA聚合酶ε参与前导链DNA复制。
Yeast DNA polymerase epsilon participates in leading-strand DNA replication.
作者信息
Pursell Zachary F, Isoz Isabelle, Lundström Else-Britt, Johansson Erik, Kunkel Thomas A
机构信息
Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA.
出版信息
Science. 2007 Jul 6;317(5834):127-30. doi: 10.1126/science.1144067.
Abstract
Multiple DNA polymerases participate in replicating the leading and lagging strands of the eukaryotic nuclear genome. Although 50 years have passed since the first DNA polymerase was discovered, the identity of the major polymerase used for leading-strand replication is uncertain. We constructed a derivative of yeast DNA polymerase epsilon that retains high replication activity but has strongly reduced replication fidelity, particularly for thymine-deoxythymidine 5'-monophosphate (T-dTMP) but not adenine-deoxyadenosine 5'-monophosphate (A-dAMP) mismatches. Yeast strains with this DNA polymerase epsilon allele have elevated rates of T to A substitution mutations. The position and rate of these substitutions depend on the orientation of the mutational reporter and its location relative to origins of DNA replication and reveal a pattern indicating that DNA polymerase epsilon participates in leading-strand DNA replication.
摘要
多种DNA聚合酶参与真核细胞核基因组前导链和后随链的复制。尽管自首个DNA聚合酶被发现以来已过去50年，但用于前导链复制的主要聚合酶的身份仍不确定。我们构建了一种酵母DNA聚合酶ε衍生物，它保留了高复制活性，但复制保真度大幅降低，尤其是对于胸腺嘧啶 - 脱氧胸苷5'-单磷酸（T-dTMP）错配，而对腺嘌呤 - 脱氧腺苷5'-单磷酸（A-dAMP）错配则不然。携带这种DNA聚合酶ε等位基因的酵母菌株中，T到A的替换突变率升高。这些替换的位置和速率取决于突变报告基因的方向及其相对于DNA复制起点的位置，并揭示了一种模式，表明DNA聚合酶ε参与前导链DNA复制。
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