Solution structure of a DNA decanter duplex containing the stable 3′ T•G base pair of the pyrimidine(6-4)pyrimidone photoproduct [(6-4) adduct]:: Implications for the highly specific 3′ T→C transition of the (6-4) adduct
Solution structure of a DNA decanter duplex containing the stable 3′ T•G base pair of the pyrimidine(6-4)pyrimidone photoproduct [(6-4) adduct]:: Implications for the highly specific 3′ T→C transition of the (6-4) adduct
复制标题
DOI：
10.1073/pnas.96.12.6632
复制
发表时间：
1999-06-08
影响因子：
11.1
通讯作者：
Choi, BS
中科院分区：
文献类型：
--
作者：
Lee, JH;Hwang, GS;Choi, BS
嘧啶（6-4）嘧啶酮光产物[（6-4）加合物]是紫外线照射DNA诱导的主要光产物之一，发生在TpT位点。（6-4）加合物是高度致突变的，并且最常导致具有85%复制错误频率的3' T -> C转变[LeClerc，J.E.，Borden，A.和Lawrence，C，W，（1991）Proc. Natl，Acad，Sci，USA 88，9685-9689]。为了确定（6-4）加合物的特异性3' T →> C跃迁的起源，我们使用实验NMR限制和分子动力学来确定（6-4）-损伤DNA十聚体双链体的溶液结构，该双链体在3' T残基和相对的G残基之间含有错配的碱基对.正常的沃森-克里克型氢键保留在病变部位的5' T处。3' T残基的O2羰基与相对的C残基的亚氨基和氨基质子形成氢键。这种潜在的氢键稳定了整个螺旋，并将（6-4）加合物的高度扭曲构象恢复为典型的B型样DNA结构。这一结构特征可以解释在跨损伤合成过程中对（6-4）损伤的5' T对面的A残基和3' T对面的G残基的插入的显著偏好。因此，这些插入产生了主要的3' T →> C转换.
The pyrimidine(6-4)pyrimidone photoproduct [(6-4) adduct] is one of the major photoproducts induced by UV irradiation of DNA and occurs at TpT sites. The (6-4) adduct is highly mutagenic and leads most often to a 3' T --> C transition with 85% replicating error frequency [LeClerc, J E,, Borden, A. & Lawrence, C, W, (1991) Proc. Natl, Acad, Sci, USA 88, 9685-9689]. To determine the origin of the specific 3' T --> C transition of the (6-4) adduct, we have used experimental NMR restraints and molecular dynamics to determine the solution structure of a (6-4)-lesion DNA decamer duplex that contains a mismatched base pair between the 3' T residue and an opposed G residue. Normal Watson-Crick-type hydrogen bonding is retained at the 5' T of the lesion site. The O2 carbonyl of the 3' T residue forms hydrogen bonds with the imino and amino protons of the opposed C residue. This potential hydrogen bonding stabilizes the overall helix and restores the highly distorted conformation of the (6-4) adduct to the typical B-form-like DNA structure. This structural feature can explain the marked preference for the insertion of an A residue opposite the 5' T and a G residue opposite the 3' T of the (6-4) lesion during trans-lesion synthesis. Thus these insertions yield the predominant 3' T --> C transition.