One of the most common DNA lesions is created when reactive oxygen alters guanine. 8-oxo-guanine may bind in the anti-conformation with an opposing cytosine or in the syn-conformation with an opposing adenine paired by transversion, and both conformations may alter DNA stability. Here we use optical tweezers to measure the stability of DNA hairpins containing 8-oxoguanine (8oxoG) lesions, comparing the results to predictive models of base-pair energies in the absence of the lesion. Contrasted with either a canonical guanine-cytosine or adenine-thymine pair, an 8oxoG-cytosine base pair shows significant destabilization of several k_BT. The magnitude of destabilization is comparable to guanine-thymine ‘wobble’ and cytosine-thymine mismatches. Furthermore, the measured energy of 8oxoG-adenine corresponds to theoretical predictions for guanine-adenine pairs, indicating that oxidative damage does not further destabilize this mismatch in our experiments, in contrast to some previous observations. These results support the hypothesis that oxidative damage to guanine subtly alters the direction of the guanine dipole, base stacking interactions, the local backbone conformation, and the hydration of the modified base. This localized destabilization under stress provides additional support for proposed mechanisms of enzyme repair.

中文翻译：

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通过单分子DNA拉伸定量氧化损伤的DNA的稳定性

当活性氧改变鸟嘌呤时，会产生一种最常见的DNA损伤。-8-氧代鸟嘌呤可以在结合抗-conformation与相对的胞嘧啶或顺式与由成对的颠换相对腺嘌呤-conformation，并且这两种构型可以改变DNA的稳定性。在这里，我们使用光镊来测量包含8-氧代鸟嘌呤（8oxoG）损伤的DNA发夹的稳定性，并将结果与​​不存在病灶的碱基对能量的预测模型进行比较。与经典的鸟嘌呤-胞嘧啶或腺嘌呤-胸腺嘧啶对相比，8oxoG-胞嘧啶碱基对显示出几k _B的显着去稳定作用T.不稳定的程度可与鸟嘌呤-胸腺嘧啶的“错配”和胞嘧啶-胸腺嘧啶的错配相媲美。此外，测得的8oxoG-腺嘌呤能量对应于鸟嘌呤-腺嘌呤对的理论预测，表明与我们之前的一些观察相反，氧化损伤并没有进一步破坏这种失配的稳定性。这些结果支持以下假设：对鸟嘌呤的氧化损伤可微妙地改变鸟嘌呤偶极子的方向，碱基堆积相互作用，局部骨架构象和修饰碱基的水合。这种在压力下的局部去稳定化为提议的酶修复机制提供了额外的支持。