Solution structure of the DNA decamer duplex containing a 3′-T.T base pair of the cis-syn cyclobutane pyrimidine dimer: implication for the mutagenic property of the cis-syn dimer
Solution structure of the DNA decamer duplex containing a 3′-T.T base pair of the cis-syn cyclobutane pyrimidine dimer: implication for the mutagenic property of the cis-syn dimer
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DOI：
10.1093/nar/28.8.1794
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发表时间：
2000-04-15
影响因子：
14.9
通讯作者：
Choi, Byong-Seok
中科院分区：
文献类型：
--
作者：
Lee, Joon-Hwa;Choi, Yun-Jeong;Choi, Byong-Seok
顺式二聚体是紫外光照射产生的主要DNA光产物。为了确定顺式-syn二聚体的致突变性质的起源，我们使用NMR限制和分子动力学来确定在顺式-syn二聚体的3 '-T和相对的T残基之间含有摆动对的DNA十聚体双链体（CS/TA双链体）的溶液结构。CS/TA双链体的溶液结构显示，顺式-syn二聚体的3 '-T.T碱基对具有与典型的Watson-Crick碱基对显著不同的碱基对几何形状，并导致其3'-区域的不稳定和构象畸变。然而，在该相关DNA十聚体内的顺式-syn二聚体处的3 '-T. A碱基对保持正常的沃森-克里克碱基对几何形状，并且在其3'-侧的构象中几乎不引起畸变。我们的研究结果表明，尽管它的稳定的氢键，T残基的插入相对于3 '-T的顺式-syn二聚体的抑制由3'-T.T碱基对引起的结构畸变。这可以解释为什么3 '-T. A颠换的频率，这是由顺式-syn二聚体产生的主要突变，
The cis-syn dimer is the major DNA photoproduct produced by UV irradiation. In order to determine the origin of the mutagenic property of the cis-syn dimer, we used NMR restraints and molecular dynamics to determine the solution structure of a DNA decamer duplex containing a wobble pair between the 3'-T of the cis-syn dimer and the opposite T residue (CS/TA duplex). The solution structure of the CS/TA duplex revealed that the 3'-T.T base pair of the cis-syn dimer had base pair geometry that was significantly different from the canonical Watson-Crick base pair and caused destabilization and conformational distortion of its 3'-region. However, a 3'-T.A base pair at the cis-syn dimer within this related DNA decamer maintains the normal Watson-Crick base pair geometry and causes little distortion in the conformation of its 3'-side. Our results show that in spite of its stable hydrogen bonding, the insertion of a T residue opposite the 3'-T of the cis-syn dimer is inhibited by structural distortion caused by the 3'-T.T base pair. This may explain why the frequency of the 3'-T.A transversion, which is the major mutation produced by the cis-syn dimer, is only