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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Shi, H; Kimsey, IJ; Gu, S; Liu, H-F; Pham, U; Schumacher, MA; Al-Hashimi, HM

Published Date

  • December 2, 2021

Published In

Volume / Issue

  • 49 / 21

Start / End Page

  • 12540 - 12555

PubMed ID

  • 34792150

Pubmed Central ID

  • PMC8643651

Electronic International Standard Serial Number (EISSN)

  • 1362-4962

Digital Object Identifier (DOI)

  • 10.1093/nar/gkab936


  • eng

Conference Location

  • England