Revealing A-T and G-C Hoogsteen base pairs in stressed protein-bound duplex DNA

Nucleic Acids Res. 2021 Dec 2;49(21):12540-12555. doi: 10.1093/nar/gkab936.

Abstract

Watson-Crick base pairs (bps) are the fundamental unit of genetic information and the building blocks of the DNA double helix. However, A-T and G-C can also form alternative 'Hoogsteen' bps, expanding the functional complexity of DNA. We developed 'Hoog-finder', which uses structural fingerprints to rapidly screen Hoogsteen bps, which may have been mismodeled as Watson-Crick in crystal structures of protein-DNA complexes. We uncovered 17 Hoogsteen bps, 7 of which were in complex with 6 proteins never before shown to bind Hoogsteen bps. The Hoogsteen bps occur near mismatches, nicks and lesions and some appear to participate in recognition and damage repair. Our results suggest a potentially broad role for Hoogsteen bps in stressed regions of the genome and call for a community-wide effort to identify these bps in current and future crystal structures of DNA and its complexes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Pairing*
  • Base Sequence
  • Binding Sites / genetics
  • Computational Biology / methods
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Databases, Genetic
  • Hydrogen Bonding
  • Models, Molecular
  • Mutation
  • Nucleic Acid Conformation*
  • Protein Binding
  • Protein Domains*
  • Thermodynamics

Substances

  • DNA-Binding Proteins
  • DNA