Modulation of Hoogsteen dynamics on DNA recognition.

Published

Journal Article

In naked duplex DNA, G-C and A-T Watson-Crick base pairs exist in dynamic equilibrium with their Hoogsteen counterparts. Here, we used nuclear magnetic resonance (NMR) relaxation dispersion and molecular dynamics (MD) simulations to examine how Watson-Crick/Hoogsteen dynamics are modulated upon recognition of duplex DNA by the bisintercalator echinomycin and monointercalator actinomycin D. In both cases, DNA recognition results in the quenching of Hoogsteen dynamics at base pairs involved in intermolecular base-specific hydrogen bonds. In the case of echinomycin, the Hoogsteen population increased 10-fold for base pairs flanking the chromophore most likely due to intermolecular stacking interactions, whereas actinomycin D minimally affected Hoogsteen dynamics at other sites. Modulation of Hoogsteen dynamics at binding interfaces may be a general phenomenon with important implications for DNA-ligand and DNA-protein recognition.

Full Text

Duke Authors

Cited Authors

  • Xu, Y; McSally, J; Andricioaei, I; Al-Hashimi, HM

Published Date

  • April 16, 2018

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 1473 -

PubMed ID

  • 29662229

Pubmed Central ID

  • 29662229

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

International Standard Serial Number (ISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-03516-1

Language

  • eng