Widespread transient Hoogsteen base pairs in canonical duplex DNA with variable energetics

Heidi S. Alvey, Federico L. Gottardo, Evgenia N. Nikolova and Hashim M. Al-Hashimi ()
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Heidi S. Alvey: University of Michigan
Federico L. Gottardo: University of Michigan
Evgenia N. Nikolova: The Scripps Research Institute
Hashim M. Al-Hashimi: Duke University School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: Abstract Hoogsteen (HG) base pairing involves a 180° rotation of the purine base relative to Watson–Crick (WC) base pairing within DNA duplexes, creating alternative DNA conformations that can play roles in recognition, damage induction and replication. Here, using nuclear magnetic resonance R1ρ relaxation dispersion, we show that transient HG base pairs occur across more diverse sequence and positional contexts than previously anticipated. We observe sequence-specific variations in HG base pair energetic stabilities that are comparable with variations in WC base pair stability, with HG base pairs being more abundant for energetically less favourable WC base pairs. Our results suggest that the variations in HG stabilities and rates of formation are dominated by variations in WC base pair stability, suggesting a late transition state for the WC-to-HG conformational switch. The occurrence of sequence and position-dependent HG base pairs provide a new potential mechanism for achieving sequence-dependent DNA transactions.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5786

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DOI: 10.1038/ncomms5786

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