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

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.

SUBMITTER: Shi H

PROVIDER: S-EPMC8643651 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Shi Honglue H Kimsey Isaac J IJ Gu Stephanie S Liu Hsuan-Fu HF Pham Uyen U Schumacher Maria A MA Al-Hashimi Hashim M HM

Nucleic acids research 20211201 21

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 ...[more]

PMID: 34792150

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