Transient Hoogsteen base pairs in canonical duplex DNA.

Published

Journal Article

Sequence-directed variations in the canonical DNA double helix structure that retain Watson-Crick base-pairing have 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.

Full Text

Duke Authors

Cited Authors

  • Nikolova, EN; Kim, E; Wise, AA; O'Brien, PJ; Andricioaei, I; Al-Hashimi, HM

Published Date

  • February 2011

Published In

Volume / Issue

  • 470 / 7335

Start / End Page

  • 498 - 502

PubMed ID

  • 21270796

Pubmed Central ID

  • 21270796

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature09775

Language

  • eng