Widespread transient Hoogsteen base pairs in canonical duplex DNA with variable energetics.
Widespread transient Hoogsteen base pairs in canonical duplex DNA with variable energetics.
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DOI：
10.1038/ncomms5786
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发表时间：
2014-09-04
影响因子：
16.6
通讯作者：
Al-Hashimi HM
中科院分区：
文献类型：
--
作者：
Alvey HS;Gottardo FL;Nikolova EN;Al-Hashimi HM
Hoogsteen碱基配对涉及DNA双链体内嘌呤碱基相对于Watson-Crick碱基配对的180度旋转，创建可在识别、损伤诱导和复制中发挥作用的替代DNA构象。在这里，使用核磁共振R1ρ弛豫色散，我们证明了瞬时胡格斯汀碱基对发生在比先前预期更多不同的序列和位置背景中。我们观察到Hoogsteen碱基对能量稳定性的序列特异性变异，这与Watson-Crick碱基对稳定性的变异相当，对于能量不太有利的Watson-Crick碱基对，Hoogsteen碱基对更加丰富。我们的结果表明，Hoogsteen稳定性和形成速率的变化是由Watson-Crick碱基对稳定性的变化主导的，这表明Watson-Crick到Hoogsteen构象开关的过渡状态较晚。序列和位置相关的Hoogsteen碱基对的出现为实现序列相关的DNA交易提供了一种新的潜在机制。
Hoogsteen base-pairing involves a 180 degree rotation of the purine base relative to Watson-Crick base-pairing within DNA duplexes, creating alternative DNA conformations that can play roles in recognition, damage induction, and replication. Here, using Nuclear Magnetic Resonance R1ρ relaxation dispersion, we show that transient Hoogsteen base-pairs occur across more diverse sequence and positional contexts than previously anticipated. We observe sequence-specific variations in Hoogsteen base-pair energetic stabilities that are comparable to variations in Watson-Crick base-pair stability, with Hoogsteen base-pairs being more abundant for energetically less favorable Watson-Crick base-pairs. Our results suggest that the variations in Hoogsteen stabilities and rates of formation are dominated by variations in Watson-Crick base pair stability, suggesting a late transition state for the Watson-Crick to Hoogsteen conformational switch. The occurrence of sequence and position-dependent Hoogsteen base-pairs provide a new potential mechanism for achieving sequence-dependent DNA transactions.