Probing Watson-Crick and Hoogsteen base pairing in duplex DNA using dynamic nuclear polarization solid-state NMR spectroscopy.

Journal Article (Journal Article)

The majority of base pairs in double-stranded DNA exist in the canonical Watson-Crick geometry. However, they can also adopt alternate Hoogsteen conformations in various complexes of DNA with proteins and small molecules, which are key for biological function and mechanism. While detection of Hoogsteen base pairs in large DNA complexes and assemblies poses considerable challenges for traditional structural biology techniques, we show here that multidimensional dynamic nuclear polarization-enhanced solid-state NMR can serve as a unique spectroscopic tool for observing and distinguishing Watson-Crick and Hoogsteen base pairs in a broad range of DNA systems based on characteristic NMR chemical shifts and internuclear dipolar couplings. We illustrate this approach using a model 12-mer DNA duplex, free and in complex with the antibiotic echinomycin, which features two central adenine-thymine base pairs with Watson-Crick and Hoogsteen geometry, respectively, and subsequently extend it to the ∼200 kDa Widom 601 DNA nucleosome core particle.

Full Text

Duke Authors

Cited Authors

  • Conroy, DW; Xu, Y; Shi, H; Gonzalez Salguero, N; Purusottam, RN; Shannon, MD; Al-Hashimi, HM; Jaroniec, CP

Published Date

  • July 26, 2022

Published In

Volume / Issue

  • 119 / 30

Start / End Page

  • e2200681119 -

PubMed ID

  • 35857870

Pubmed Central ID

  • PMC9335254

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.2200681119


  • eng

Conference Location

  • United States