酵母 DNA 聚合酶 η 实现无差错复制氧化损伤 DNA 的结构基础。
Structural basis for error-free replication of oxidatively damaged DNA by yeast DNA polymerase η.
机构信息
Department of Structural & Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA.
出版信息
Structure. 2010 Nov 10;18(11):1463-70. doi: 10.1016/j.str.2010.08.019.
Abstract
7,8-dihydro-8-oxoguanine (8-oxoG) adducts are formed frequently by the attack of oxygen-free radicals on DNA. They are among the most mutagenic lesions in cells because of their dual coding potential, where, in addition to normal base-pairing of 8-oxoG(anti) with dCTP, 8-oxoG in the syn conformation can base pair with dATP, causing G to T transversions. We provide here for the first time a structural basis for the error-free replication of 8-oxoG lesions by yeast DNA polymerase η (Polη). We show that the open active site cleft of Polη can accommodate an 8-oxoG lesion in the anti conformation with only minimal changes to the polymerase and the bound DNA: at both the insertion and post-insertion steps of lesion bypass. Importantly, the active site geometry remains the same as in the undamaged complex and provides a basis for the ability of Polη to prevent the mutagenic replication of 8-oxoG lesions in cells.
摘要
7,8-二氢-8-氧鸟嘌呤（8-oxoG）加合物是由氧自由基攻击 DNA 频繁形成的。由于其双重编码潜力，它们是细胞中最具突变性的损伤之一，除了 8-oxoG（反）与 dCTP 的正常碱基配对外，顺式构象中的 8-oxoG 可以与 dATP 碱基配对，导致 G 到 T 的颠换。我们在这里首次为酵母 DNA 聚合酶 η（Polη）无差错复制 8-oxoG 损伤提供了结构基础。我们表明，Polη 的开放活性位点裂隙可以容纳反式构象的 8-oxoG 损伤，而聚合酶和结合的 DNA 只有最小的变化：在损伤绕过的插入和插入后步骤。重要的是，活性位点的几何形状与未受损复合物相同，为 Polη 防止细胞中 8-oxoG 损伤的诱变复制提供了基础。
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