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.
中科院分区:
文献类型:
--
作者:
Nikolova, Evgenia N.;Kim, Eunae;Wise, Abigail A.;O'Brien, Patrick J.;Andricioaei, Ioan;Al-Hashimi, Hashim M.
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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