Transient Hoogsteen base pairs in canonical duplex DNA.

Transient Hoogsteen base pairs in canonical duplex DNA.
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DOI:
10.1038/nature09775
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发表时间:
2011-02-24
期刊:
影响因子:
64.8
通讯作者:
Al-Hashimi, Hashim M.
Al-Hashimi, Hashim M.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Nikolova, Evgenia N.;Kim, Eunae;Wise, Abigail A.;O'Brien, Patrick J.;Andricioaei, Ioan;Al-Hashimi, Hashim M.

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标准DNA双螺旋结构中的序列定向变异保留了Watson-Crick碱基配对,在DNA识别、拓扑和核小体定位方面发挥着重要作用。通过使用核磁共振弛豫色散谱与定向分子动力学模拟相结合,我们观察到在规范双链DNA内的CA和TA步长从Watson-Crick碱基对向低密度和短寿命的A·T和G·C Hoogsteen碱基对的瞬时序列漂移。对转录因子特异结合的DNA双链和受损DNA位点中Hoogsteen碱基对的观察表明,DNA双螺旋固有地编码激发态Hoogsteen碱基对,作为一种将其结构复杂性扩展到基于Watson-Crick碱基配对的手段。这里提出的方法为表征瞬时低密度核酸结构提供了一条新的途径,我们预测这种结构将在基因组中大量存在,并构成遗传密码的第二个瞬时层。
Sequence-directed variations in the canonical DNA double helix structure that retain Watson-Crick base-pairing play important roles in DNA recognition, topology, and nucleosome positioning. By using nuclear magnetic resonance relaxation dispersion spectroscopy in concert with steered molecular dynamics simulations, we have observed transient sequence-specific excursions away from Watson-Crick base-pairing at CA and TA steps inside canonical duplex DNA towards low-populated and short-lived A•T and G•C Hoogsteen base-pairs. The observation of Hoogsteen base-pairs in DNA duplexes specifically bound to transcription factors and in damaged DNA sites implies that the DNA double helix intrinsically codes for excited state Hoogsteen base-pairs as a means of expanding its structural complexity beyond that which can be achieved based on Watson-Crick base-pairing. The methods presented here provide a new route for characterizing transient low-populated nucleic acid structures, which we predict will be abundant in the genome and constitute a second transient layer of the genetic code.
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